Rare coding variants in ten genes confer substantial risk for schizophrenia.

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

Beyond the waves: Unraveling pandemic outcomes with genomic insights and immunity analysis - Evidence from 14 countries.

OBJECTIVE: Although the World Health Organization and many governments have recategorized COVID-19 as a generally mild to moderately severe disease, consecutive pandemic waves driven by immune escape variants have underscored the need for timely and accurate prediction of the next outbreak. Nevertheless, little attention has been paid to translating genomic data and infection- and vaccine-induced immunity into direct estimates. METHODS: We retrieved epidemiologic and genomic data shortly before pandemic waves across 14 developed countries from late 2021 to mid-2022 and examined associations between early-stage variant competition, infection- and vaccine-induced immunity, and the time intervals between wave peaks. We applied regression analysis and the generalized estimating equation method to construct an inferential model. RESULTS: Each per cent increase in the proportion of a new variant was associated with a 1.0% reduction in interpeak intervals on average. Curvilinear associations between vaccine-induced immunity and outcome variables were observed, suggesting that reaching a critical vaccine distribution rate may decrease the caseload of the upcoming wave. CONCLUSIONS: By leveraging readily accessible pre-outbreak genomic and epidemiologic data, our results not only substantiate the predictive potential of early variant fractions but also propose that immunity acquired through infection alone may not sufficiently mitigate transmission. Conversely, a rapid and widespread vaccination initiative appears to be correlated with a decrease in disease incidence.

Trimester-specific association between fetal growth and physical activity in pregnant women: total physical activity vs moderate-to-vigorous exercise.

OBJECTIVE: To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders. METHODS: We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth. RESULTS: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. CONCLUSIONS: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Deciphering the in situ phonon evolution of potassium sodium niobate under varying temperature and electric fields.

The application of in situ Raman spectroscopy under multiple fields is widely recognized as an effective approach for investigating the physical mechanism of phase transitions in ferroelectrics, because it can directly provide the detailed information about the vibration evolution of various phonon modes within lattices, such as bond stretching and rotation. Based on this technique, our work aims to thoroughly probe the dynamics of phase transitions in traditional ferroelectric potassium sodium niobate [(K,Na)NbO3, KNN] under external fields, by analyzing the in situ dependence of wavenumber and intensity of phonon modes under the varying temperature and electric fields. The results indicate that different vibration modes respectively relating to the A-site ions and NbO6 octahedra in KNN exhibit distinct and abrupt distortion behavior during the orthorhombic-tetragonal and tetragonal-cubic transitions. Moreover, a certain degree of distortion can still be observed in the cubic phase above the Curie temperature. With an applied electric field, KNN presents quite different electrostriction in orthorhombic and tetragonal phases. Particularly, more than one kind of phonon mode undergoes non-linear variations under the varying electric fields, accompanied by the mutations at some fixed fields. These findings will be conducive to further understanding the phase transition mechanism in KNN from the perspective of phonon evolution. Simultaneously, it will also give crucial guidance for the design and development of KNN-based ferroelectrics as well as functional devices.

Validation of self-reported medical condition in the Taiwan Biobank.

BACKGROUND: This study aimed to validate self-reported medical conditions in the Taiwan Biobank (TWBB), in which participants were inquired about 30 disease conditions, by comparing them with claims records from Taiwan's National Health Insurance (NHI) claims database. METHODS: We identified 30 clinical diagnoses using ICD-CM codes from ambulatory and hospital claims within the NHI claims database, matching diseases included in the TWBB. The concordance between self-reports and claims records was evaluated using tetrachoric correlation to assess the correlation between binary variables. RESULTS: A total of 131,834 participants aged 30-70 years with data from the TWBB and NHI records were included. Concordance analysis revealed tetrachoric correlations ranged from 0.420 (chronic obstructive pulmonary disease) to 0.970 (multiple sclerosis). However, several disorders exhibited lower tetrachoric correlations. The concordance was higher among those with higher education attainment, and lower among married individuals. CONCLUSION: The concordance between self-reports in the TWBB and NHI claims records varied across clinical diagnoses, showing inconsistencies depending on participant characteristics. These findings underscore the need for further investigation, especially when these variables are crucial to research objectives. Integrating complementary databases such as clinical diagnoses, prescription records, and medical procedures can enhance accuracy through customized algorithms based on disease categories and participant characteristics and optimize sensitivity or positive predictive values to align with specific research objectives.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

COVID-19 control measures unexpectedly increased the duration of stay at High Speed Rail stations during the first community outbreak in Taiwan.

During the COVID-19 pandemic, Taiwan has implemented strict border controls and community spread prevention measures. As part of these efforts, the government also implemented measures for public transportation. In Taiwan, there are two primary public transportation systems: Taiwan Railways (TR) is commonly utilized for local travel, while the Taiwan High-Speed Rail (THSR) is preferred for business trips and long-distance journeys due to its higher speed. In this study, we examined the impact of these disease prevention measures on the number of passengers and duration of stay in two major public transportation systems during the first community outbreak from April 29th to May 29th, 2021. Using data from a local telecommunications company, our study observed an expected decrease in the number of passengers after the cancellation of non-reserved seats at both TR and THSR stations across all 19 cities in the main island of Taiwan. Surprisingly, however, the duration of stay in some of the cities unexpectedly increased, especially at THSR stations. This unanticipated rise in the duration of stay has the potential to elevate contact probability among passengers and, consequently, the transmission rate. Our analysis shows that intervention policies may result in unforeseen outcomes, highlighting the crucial role of human mobility data as a real-time reference for policymakers. It enables them to monitor the impact of disease prevention measures and facilitates informed, data-driven decision-making.

Obstetric outcomes in Jehovah's Witnesses: case series over nine years in a London teaching hospital.

OBJECTIVES: The aim of the study is to assess obstetric and fetal outcomes of Jehovah's Witnesses (JWs) mothers in an inner city teaching hospital, as well as to examine the acceptance rates of various blood fractions and blood transfusion alternatives. METHODS: Case series to evaluate the maternal and fetal outcomes of JWs over a nine period between 2013 and 2021. RESULTS: There were 146 pregnancies extracted from our database, of which 10 were early pregnancy losses. Data from 136 deliveries > 24 weeks' gestation were assessed, with a mean maternal age and gestational age of 30.26 (± 5.4) years and 38.7 (± 5.3) weeks, respectively. 57% had normal vaginal deliveries, 8% had instrumental births and 35% had caesarean births. Mean estimated blood loss at caesarean was 575 (± 305.6) mls, while the overall mean estimated loss was 427.8 (± 299.8) mls. Cell salvage was performed in all caesarean sections but autologous transfusion was only necessary for 26%. Consultant presence was documented in 62% of caesarean births. The mean birthweight and 5-min Apgar scores were 3.31 (± 0.05) kg and 9.1 (± 0.09), respectively. There were no maternal deaths or admissions to the adult intensive care unit and the most serious complication was a uterine rupture following a trial of scar, after which the baby required cooling for hypoxic ischaemic encephalopathy. CONCLUSIONS: Pregnant JWs received obstetric care led by senior clinicians, with optimisation of haematinics, minimizing of blood loss at delivery and access to technology such as cell salvage.

[TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

[Intraductal carcinomas of the salivary glands: a clinicopathological and molecular genetic analysis of twenty-seven cases].

Objective: To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands. Methods: Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People's Hospital and two cases from Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed. Results: There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption. Conclusions: IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)µg/L(range: 1.4 to 13.4 µg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

[Analysis of the relationship between solar greenhouse operation and occupational high incidence diseases].

Objective: To understand the health status of solar greenhouse workers, to provide scientific basis for the development of occupational high incidence diseases prevention and control strategies. Methods: In July 2019, a random cluster sampling method was used to select 245 workers engaged in solar greenhouse vegetable cultivation in Daba Village, Jingyuan County, Baiyin City, Gansu Province as the solar greenhouse operation group. Matched by gender, age, marital status, body mass index (BMI), 282 people from adjacent Shaliang Village who did not engage in solar greenhouse operation were selected as the control group. Field investigation and health examination were carried out among the study subjects. The general situation, facial features examination results, ophthalmic examination results, bone and joint examination results and skin examination results were compared between the two groups. And the multiple logistic regression analysis was used to analyze the influencing factors of abnormal bone and joint examination (upper limbs, lower limbs, hands and spine bone joints) in study subjects. Results: There were statistically significant differences in smoking age and alcohol consumption between the two groups (P<0.001). Compared with the control group, the abnormal detection rates of nose examination, throat examination, slit lamp examination, conjunctival examination, lower limb bone joint examination, hand bone joint examination, spine examination, head and neck skin examination, trunk skin examination, upper limb skin examination, and lower limb skin examination in the solar greenhouse operation group were higher, and the differences were statistically significant (χ(2)=11.53, 7.94, 9.92, 27.93, 79.32, 81.42, 9.43, 6.79, 9.76, 4.34, 8.29, P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, age, marital status, education level, BMI, compared with the control group, solar greenhouse operation was a risk factor for abnormal bone and joint examination (OR=1.178, 95%CI: 1.151-2.143, P=0.001) . Conclusion: Solar greenhouse operation has a certain harmful effect on health of workers, and solar greenhouse workers have an increased risk of abnormal diseases of upper limbs, lower limbs, hands and spine bone joints.

Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan.

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes.

BACKGROUNDS: A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups. METHODS: This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups. RESULTS: The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups. CONCLUSIONS: Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

The use of premixed drugs in commodity packets in the population: prevalence and correlates revealed by the 2018 National Survey of Substance Use in Taiwan.

BACKGROUND: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug packet users. METHODS: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs and other psychoactive substances, among others. RESULTS: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had a lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were similar to those of the exclusive use of other drugs except that there was a lack of gender differences in the use of drugs in commodity packets but not in the exclusive use of other drugs. CONCLUSION: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug packet use.

Multidetector CT-derived tricuspid annulus measurements predict tricuspid regurgitation reduction after transcatheter aortic valve replacement.

AIM: To use multidetector row computed tomography (MDCT)-derived tricuspid annulus (TA) measurements to identify predictors for tricuspid regurgitation (TR) reduction after transcatheter aortic valve replacement (TAVR), and to investigate the impact of TR change on prognosis. MATERIALS AND METHODS: A retrospective, single-centre study was conducted on consecutive patients who underwent TAVR with concomitant baseline mild or more severe TR from April 2012 to April 2022. TA parameters were measured using MDCT. RESULTS: The study comprised 266 patients (mean age 74.2 ± 7.6 years, 147 men) and 45.1% had more than one grade of TR reduction at follow-up. Independent predictors of TR reduction at follow-up were distance between TA centroid and antero-septal commissure (odd ratio [OR] 0.776; 95% confidence interval [CI]: 0.672-0.896, p=0.001), baseline TR of moderate or worse (OR 4.599; 95% CI: 2.193-9.648, p<0.001), systolic pulmonary artery pressure (OR 1.018; 95% CI: 1.002-1.035, p=0.027), age (OR 0.955; 95% CI: 0.920-0.993, p=0.019), and pre-existing atrial fibrillation (OR 0.209; 95% CI: 0.101-0.433, p<0.001). Patients without TR reduction had higher rates of rehospitalisation (hazard ratio [HR] 0.642; 95% CI: 0.413-0.998, p=0.049). CONCLUSIONS: The MDCT-derived TA parameter was predictive of TR reduction after TAVR. Persistent TR after TAVR was associated with higher rates of rehospitalisation.

The global prevalence of premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: The objective of this review was to answer the global prevalence of premature ovarian insufficiency (POI), and explore the associated factors including etiopathology and regions with POI. METHODS: The search was conducted on reports from a total of eight databases that comprised Chinese National Knowledge Infrastructure (CNKI), Wanfang, China BioMedical Literature Database (CBM), PubMed, the Cochrane Library, Embase, Web of Science and Ovid MEDLINE® between 1946 and 2021. To analyze the source of heterogeneity, we performed subgroup analysis based on different etiologies and regions. Meta-analysis was carried out by Stata14.0 software. RESULTS: The results showed that the global overall prevalence of POI among women was 3.5%. By subgroup analysis, the prevalence of POI among women with iatrogenic etiology was 11.2%, followed by autoimmunity (10.5%); the prevalence of POI by region was 11.3% at the highest in North America followed by South America (5.4%); and the prevalence of POI was 5.3% in a developing country, higher than 3.1% in a developed country. The trend of prevalence of POI over the past 20 years was on the rise (although p > 0.05). CONCLUSION: We recommend that health and medical institutions strengthen public health awareness, achieve health-education goals related to POI and increase women's awareness of and attention to POI.

Application of machine learning algorithms to predict osteoporosis in postmenopausal women with type 2 diabetes mellitus.

PURPOSE: The screening and diagnosis of osteoporosis in patients with type 2 diabetes mellitus (T2DM) based on bone mineral density remains challenging because of the limited availability and accessibility of dual-energy X-ray absorptiometry. We aimed to develop and validate models to predict the risk of osteoporosis in postmenopausal women with T2DM based on machine learning (ML) algorithms. METHODS: This retrospective study included 303 postmenopausal women with T2DM. To develop prediction models for osteoporosis, we applied nine ML algorithms combined with demographic, clinical, and laboratory data. The least absolute shrinkage and selection operator were used to perform feature selection. We used the bootstrap resampling technique for model training and validation. To test the performance of the models, we calculated indices including the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, calibration curve, and decision curve analysis. Furthermore, we conducted fivefold cross-validation for parameter optimization and model validation. Feature importance was assessed using the SHapley additive explanation (SHAP). RESULTS: We identified 10 independent predictors as the most valuable features. An AUROC of 0.616-1.000 was observed for nine ML algorithms. The extreme gradient boosting (XGBoost) model exhibited the best performance, outperforming conventional risk assessment tools and registering 0.993 in the training set, 0.798 in the validation set, and 0.786 in the test set for fivefold cross-validation. Using SHAP, we found that the explanatory variables contributed to the model and their relationship with osteoporosis occurrence. Furthermore, we developed a user-friendly tool for calculating the risk of osteoporosis. CONCLUSIONS: With the integration of demographic and clinical risk factors, ML algorithms can accurately predict osteoporosis. The XGBoost model showed ideal performance. With the incorporation of these models in the clinic, patients may benefit from early osteoporosis diagnosis and treatment.

Comparison of the neurobehavioural profile of early-preterm infants against term and late-preterm infants using the Hammersmith neonatal neurological examination.

AIM: To compare the neurobehavioural profile of early-preterm infants (<32 weeks gestation) at term-corrected age (39+0 -41+6 weeks) versus late-preterm and full-term infants at similar term gestational ages. METHODS: Early-preterm infants were assessed neurologically at term-corrected age using the Hammersmith neonatal neurological examination. The raw scores of the 34 Hammersmith neonatal neurological examination items were converted to optimality scores. Pairwise comparison of neurobehavioural patterns between early-preterm infants at term-corrected age versus late-preterm and full-term infants at similar gestational ages were made using independent sample t tests. Differences in optimality scores between the three groups were evaluated using one-way analysis of variance. RESULTS: Sixty-eight early-preterm infants assessed at term-corrected age were compared against 75 late-preterm infants and 133 full-term infants. Mean total optimality scores (±standard deviation) of early-preterm, late-preterm and full-term infants at term-corrected age were 27.68 (±3.97), 29.09 (±2.45) and 31.58 (±1.39), respectively (P < 0.001). The mean optimality score of early-preterm infants was significantly lower when compared pairwise with late-preterm infants and full-term infants with mean difference of -1.42 (P = 0.013) and -3.91 (P < 0.001), respectively. CONCLUSION: The neurobehavioural profile of early-preterm infants lags significantly behind those of late-preterm and full-term infants at term-corrected age. This study also provides reference raw and optimality scores for all items in the Hammersmith neonatal neurological examination for early-preterm infants in a predominantly Asian population.

Chemical and Cellular Formation of Reactive Oxygen Species from Secondary Organic Aerosols in Epithelial Lining Fluid.

INTRODUCTION: Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5). PM2.5 inhalation and deposition into the respiratory tract causes the formation of ROS by chemical reactions and phagocytosis of macrophages in the epithelial lining fluid (ELF), but their relative contributions are not well quantified and their link to oxidative stress remains uncertain. The specific aims of this project were (1) elucidating the chemical mechanism and quantifying the formation kinetics of ROS in the ELF by SOA; (2) quantifying the relative importance of ROS formation by chemical reactions and macrophages in the ELF. METHODS: SOA particles were generated using reaction chambers from oxidation of various precursors including isoprene, terpenes, and aromatic compounds with or without nitrogen oxides (NOx). We collected size-segregated PM at two highway sites in Anaheim, CA, and Long Beach, CA, and at an urban site in Irvine, CA, during two wildfire events. The collected particles were extracted into water or surrogate ELF that contained lung antioxidants. ROS generation was quantified using electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping technique. PM oxidative potential (OP) was also quantified using the dithiothreitol assay. In addition, kinetic modeling was applied for analysis and interpretation of experimental data. Finally, we quantified cellular superoxide release by RAW264.7 macrophage cells upon exposure to quinones and isoprene SOA using a chemiluminescence assay as calibrated with an EPR spin-probing technique. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. RESULTS: Superoxide radicals (·O2-) were formed from aqueous reactions of biogenic SOA generated by hydroxy radical (·OH) photooxidation of isoprene, ß-pinene, α-terpineol, and d-limonene. The temporal evolution of ·OH and ·O2- formation was elucidated by kinetic modeling with a cascade of aqueous reactions, including the decomposition of organic hydroperoxides (ROOH), ·OH oxidation of primary or secondary alcohols, and unimolecular decomposition of α-hydroxyperoxyl radicals. Relative yields of various types of ROS reflected the relative abundance of ROOH and alcohols contained in SOA, which generated under high NOx conditions, exhibited lower ROS yields. ROS formation by SOA was also affected by pH. Isoprene SOA had higher ·OH and organic radical yields at neutral than at acidic pH. At low pH ·O2- was the dominant species generated by all types of SOA. At neutral pH, α-terpineol SOA exhibited a substantial yield of carbon-centered organic radicals (R·), while no radical formation was observed by aromatic SOA.Organic radicals in the ELF were formed by mixtures of Fe2+ and SOA generated from photooxidation of isoprene, α-terpineol, and toluene. The molar yields of organic radicals by SOA were 5-10 times higher in ELF than in water. Fe2+ enhanced organic radical yields by a factor of 20-80. Ascorbate mediated redox cycling of iron ions and sustained organic peroxide decomposition, as supported by kinetic modeling reproducing time- and concentration-dependence of organic radical formation, as well as by additional experiments observing the formation of Fe2+ and ascorbate radicals in mixtures of ascorbate and Fe3+. ·OH and superoxide were found to be efficiently scavenged by antioxidants.Wildfire PM mainly generated ·OH and R· with minor contributions from superoxide and oxygen-centered organic radicals (RO·). PM OP was high in wildfire PM, exhibiting very weak correlation with radical forms of ROS. These results were in stark contrast with PM collected at highway and urban sites, which generated much higher amounts of radicals dominated by ·OH radicals that correlated well with OP. By combining field measurements of size-segregated chemical composition, a human respiratory tract model, and kinetic modeling, we quantified production rates and concentrations of different types of ROS in different regions of the ELF by considering particle-size-dependent respiratory deposition. While hydrogen peroxide (H2O2) and ·O2- production were governed by Fe and Cu ions, ·OH radicals were mainly generated by organic compounds and Fenton-like reactions of metal ions. We obtained mixed results for correlations between PM OP and ROS formation, providing rationale and limitations of the use of oxidative potential as an indicator for PM toxicity in epidemiological and toxicological studies.Quinones and isoprene SOA activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in macrophages, releasing massive amounts of superoxide via respiratory burst and overwhelming the superoxide formation by aqueous chemical reactions in the ELF. The threshold dose for macrophage activation was much smaller for quinones compared with isoprene SOA. The released ROS caused lipid peroxidation to increase cell membrane fluidity, inducing oxidative damage and stress. Further increases of doses led to the activation of antioxidant response elements, reducing the net cellular superoxide production. At very high doses and long exposure times, chemical production became comparably important or dominant if the escalation of oxidative stress led to cell death. CONCLUSIONS: The mechanistic understandings and quantitative information on ROS generation by SOA particles provided a basis for further elucidation of adverse aerosol health effects and oxidative stress by PM2.5. For a comprehensive assessment of PM toxicity and health effects via oxidative stress, it is important to consider both chemical reactions and cellular processes for the formation of ROS in the ELF. Chemical composition of PM strongly influences ROS formation; further investigations are required to study ROS formation from various PM sources. Such research will provide critical information to environmental agencies and policymakers for the development of air quality policy and regulation.