[Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree].

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 µmol/(L·h) or elavated Lyso-GL-3 level>1.10 µg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

It's time to regulate - The importance of accurate surgical-grade tourniquet autoregulation in blood flow restriction exercise applications.

OBJECTIVE: Evaluate the efficacy of five common blood flow restriction (BFR) systems to accurately maintain and autoregulate BFR pressure in the tourniquet cuff near target pressure throughout exercise. DESIGN: Randomised crossover design. SETTING: Laboratory. PARTICIPANTS: 15 healthy individuals. OUTCOME MEASURES: 1) Percentage of total BFR time that surgical-grade tourniquet autoregulation, defined as automatic and rapid self-regulation of cuff pressure to within ±15 mmHg of initial target pressure within 1 s in the presence of transient pressure changes associated with exercise, was provided; 2) pressure change in the BFR cuff throughout exercise, by comparing the initial target pressure to the measured pressure at completion of BFR exercise. RESULTS: One BFR system could provide surgical-grade tourniquet autoregulation for the whole duration (100 ± 0%) of the BFR exercise in all subjects. In two of the five BFR systems evaluated, measured cuff pressure at the end of exercise was not different (p < 0.05) to the initial target pressure. CONCLUSIONS: Surgical-grade tourniquet autoregulation is important to consistently and reliably apply a targeted BFR pressure stimulus. This may allow BFR methodology and protocols to be accurately implemented and controlled so that the results can be more meaningfully compared, leading to the potential optimization of applications.

COVID-19 vaccination and transmission patterns among pregnant and postnatal women during the fifth wave of COVID-19 in a tertiary hospital in Hong Kong.

INTRODUCTION: Vaccination is a key strategy to control the coronavirus disease 2019 (COVID-19) pandemic. Safety concerns strongly influence vaccine hesitancy. Disease transmission during pregnancy could exacerbate risks of preterm birth and perinatal mortality. This study examined patterns of vaccination and transmission among pregnant and postnatal women during the fifth wave of COVID-19 in Hong Kong. METHODS: The Antenatal Record System and Clinical Management System of the Hospital Authority was used to retrieve information concerning the demographic characteristics, vaccination history, COVID-19 status, and obstetric outcomes of women who were booked for delivery at Queen Mary Hospital in Hong Kong and had attended the booking antenatal visit from 1 July 2021 to 30 June 2022. RESULTS: Among 2396 women in the cohort, 2006 (83.7%), 1843 (76.9%), and 831 (34.7%) had received the first, second, and third doses of COVID-19 vaccine, respectively. Among 1012 women who had received the second dose, 684 (67.6%) women were overdue for their third dose. There were 265 (11.1%) reported COVID-19 cases. Women aged 20 to 29 years had a low vaccination rate but the highest disease rate (19.1%). The disease rate was more than tenfold higher in women who had no (20.3%) or incomplete (18.8%) vaccination, compared with women who had complete vaccination (2.1%; P<0.001). CONCLUSION: Acceptance of COVID-19 vaccination was low in pregnant women. Urgent measures are needed to promote vaccination among pregnant women before the next wave of COVID-19.

The role of high-risk HPV testing in cervical cancer surveillance.

OBJECTIVES: While high-risk HPV (hrHPV) testing is not formally recommended as a surveillance modality in patients with a history of cervical cancer, it is often performed in routine practice. It is unclear whether the presence of hrHPV infection after cervical cancer treatment is associated with recurrent disease. METHODS: Patients with a cervical cancer diagnosis who were seen in a single institution between May 2012 and December 2019 were retrospectively identified. Squamous cell, adenocarcinoma, adenosquamous, and neuroendocrine histologies were included. Those with cancer progression within 3 months of treatment or < 1 year of documented surveillance were excluded. Patients who had hrHPV testing performed were included in the primary outcome analysis. RESULTS: Of the 262 patients meeting inclusion criteria, 58 (22%) recurrences were diagnosed, and recurrence was most commonly detected by a surveillance imaging study (71%). Among the 169 patients that were tested for hrHPV during the surveillance period, 41 (24%) had at least one positive hrHPV test. Recurrent disease was diagnosed in 24 (14%). Of the 24 patients with recurrent disease, 5 (21%) had at least one positive hrHPV test during surveillance, versus 36 (24%) of 145 patients without recurrent disease (p = 0.67). No recurrences were detected by hrHPV testing. CONCLUSIONS: Positive hrHPV testing in the surveillance setting was not associated with cervical cancer recurrence but did lead to additional studies and procedures. Our findings do not support the routine use of hrHPV testing for the evaluation of cervical cancer recurrence.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

A Nonlinear Association between Neighborhood Walkability and Risks of Sarcopenia in Older Adults.

OBJECTIVES: Neighborhood walkability has been found to be positively related to physical activity and negatively associated with risks of noncommunicable diseases. However, limited studies have examined its association with sarcopenia in older adults. Thus, this study aimed to examine the association between neighborhood walk score and risks of sarcopenia in a sample of older Taiwanese adults. DESIGN AND SETTING: This study was a cross-sectional investigation using telephone-based survey. PARTICIPANTS: A nationwide telephone-based survey targeting older adults (≥ 65 years) was conducted in Taiwan. MEASUREMENTS: Data on neighborhood walkability (determined by walk score of residential neighborhood), sarcopenia scores (measured by SARC-F), and personal characteristics were obtained. The relationships between walk score and risks of sarcopenia were examined using generalized additive models. RESULTS: A total of 1,056 older adults participated in the survey. In model 1 (sex and age) and model 2 (full-adjusted model), a nonlinear association between neighborhood walk score and risks of sarcopenia was observed. Results showed that risks of sarcopenia appear to be lower in neighborhoods with a 40-walk score (Car-Dependent; most errands require a car) and an 80-walk score (Very Walkable) and highest in the neighborhood with a 60-walk score (Somewhat Walkable). CONCLUSIONS: The study revealed a nonlinear relationship between neighborhood walkability and risks of sarcopenia in older adults in Asian context. Results provided information to urban designers and public health practitioners that more walkable neighborhood may not necessarily protect older adults from risks of sarcopenia.

Heidelberg colorectal data set for surgical data science in the sensor operating room.

Image-based tracking of medical instruments is an integral part of surgical data science applications. Previous research has addressed the tasks of detecting, segmenting and tracking medical instruments based on laparoscopic video data. However, the proposed methods still tend to fail when applied to challenging images and do not generalize well to data they have not been trained on. This paper introduces the Heidelberg Colorectal (HeiCo) data set - the first publicly available data set enabling comprehensive benchmarking of medical instrument detection and segmentation algorithms with a specific emphasis on method robustness and generalization capabilities. Our data set comprises 30 laparoscopic videos and corresponding sensor data from medical devices in the operating room for three different types of laparoscopic surgery. Annotations include surgical phase labels for all video frames as well as information on instrument presence and corresponding instance-wise segmentation masks for surgical instruments (if any) in more than 10,000 individual frames. The data has successfully been used to organize international competitions within the Endoscopic Vision Challenges 2017 and 2019.

Adapting Bidirectional Encoder Representations from Transformers (BERT) to Assess Clinical Semantic Textual Similarity: Algorithm Development and Validation Study.

BACKGROUND: Natural Language Understanding enables automatic extraction of relevant information from clinical text data, which are acquired every day in hospitals. In 2018, the language model Bidirectional Encoder Representations from Transformers (BERT) was introduced, generating new state-of-the-art results on several downstream tasks. The National NLP Clinical Challenges (n2c2) is an initiative that strives to tackle such downstream tasks on domain-specific clinical data. In this paper, we present the results of our participation in the 2019 n2c2 and related work completed thereafter. OBJECTIVE: The objective of this study was to optimally leverage BERT for the task of assessing the semantic textual similarity of clinical text data. METHODS: We used BERT as an initial baseline and analyzed the results, which we used as a starting point to develop 3 different approaches where we (1) added additional, handcrafted sentence similarity features to the classifier token of BERT and combined the results with more features in multiple regression estimators, (2) incorporated a built-in ensembling method, M-Heads, into BERT by duplicating the regression head and applying an adapted training strategy to facilitate the focus of the heads on different input patterns of the medical sentences, and (3) developed a graph-based similarity approach for medications, which allows extrapolating similarities across known entities from the training set. The approaches were evaluated with the Pearson correlation coefficient between the predicted scores and ground truth of the official training and test dataset. RESULTS: We improved the performance of BERT on the test dataset from a Pearson correlation coefficient of 0.859 to 0.883 using a combination of the M-Heads method and the graph-based similarity approach. We also show differences between the test and training dataset and how the two datasets influenced the results. CONCLUSIONS: We found that using a graph-based similarity approach has the potential to extrapolate domain specific knowledge to unseen sentences. We observed that it is easily possible to obtain deceptive results from the test dataset, especially when the distribution of the data samples is different between training and test datasets.

PARPi after PARPi in epithelial ovarian cancer.

The objective of this study was to describe the treatment experience of patients with recurrent epithelial ovarian cancer who are retreated with an inhibitor of poly(ADP-ribose)-polymerase (PARPi). We conducted a multi-institutional, retrospective review of ovarian cancer patients who received ≥2 lines of therapy containing a PARPi. Demographic, clinical, and pathological data were analyzed with descriptive statistics. Twenty-two patients were identified. For initial PARPi (PARPi1), 12 patients (54.5%) received veliparib, 7 (31.8%) olaparib and 3 (13.6%) rucaparib resulting in 10 patients who had no evidence of disease at the completion of therapy (NED), 3 partial responses (PR), 4 stable disease (SD), and 3 progressive disease (PD). (All 10 CRs involved veliparib given in conjunction with cytotoxic chemotherapy). PARPi1 was used as maintenance in 2 patients. PARPi1 was discontinued because planned number of cycles was reached (n = 10), progression (n = 8), toxicity (n = 2), other (n = 2). For second PARPi (PARPi2), 10 patients (45.4%) received niraparib, 6 (27.3%) olaparib, and 6 (27.3%) rucaparib resulting in 3 PR, 13 SD, and 3 PD. PARPi2 was used as maintenance in 3 patients. The 3 patients who experienced a PR to PARPi2 had a BRCA mutation and were NED following PARPi1. PARPi2 was discontinued because of progression (n = 13), toxicity (n = 6), other (n = 2). One patient currently remains on PARPi2. Toxicity after PARPi1 was not associated with toxicity from PARPi2 (p > 0.05). With 3 approved PARPi for different indications including frontline and recurrence, the opportunity to reuse PARPi has increased. Characterizing those who should be re-challenged is an important initiative moving forward.

Sevelamer Carbonate Crystal-Induced Colitis.

Hyperphosphatemia is a common and well-described complication of end-stage renal disease. Despite strict dietary constraints and compliance, phosphate binders such as calcium acetate and/or sevelamer carbonate are also needed to treat secondary hyperparathyroidism. This case vignette describes an underrecognized adverse effect of a phosphate binder, sevelamer carbonate, inducing colitis in a 47-year-old male with insulin-dependent diabetes complicated by end-stage renal disease. He presented for recurrent abdominal pain with associated nausea and was found to have multiple circumferential lesions on computed tomography including distal ascending, transverse, and proximal descending colon. Colonoscopy demonstrated nearly obstructing lesions worrisome for colonic ischemia or inflammatory bowel disease. Pathological review of histology demonstrated ragged colonic mucosa with ulcerative debris and nonpolarizing crystalline material at the sites of ulceration, morphologically consistent with the phosphate binder, sevelamer carbonate. Sevelamer carbonate was discontinued, and the patient was transitioned to calcium carbonate with strict dietary restrictions. His symptoms improved with the cessation of sevelamer, and he was subsequently discharged home. He eventually underwent renal transplant without redevelopment of symptoms. Recognition of this underreported complication of sevelamer carbonate, phosphate binder, is of utmost importance in directing appropriate therapy with cessation of this medication in the setting of gastrointestinal complaints or more specifically enteritis and colitis. Clinicians providing care to end-stage renal patients taking either sevelamer and/or sodium polystyrene sulfonate should have increased awareness of the possible gastrointestinal side effects.

Impact of seed-applied pesticides on rhizobial survival and legume nodulation.

AIMS: Compatibility of seed-applied pesticides and rhizobial inoculants is an important consideration for farmers when sowing legumes. Some of the seed-applied pesticides may influence rhizobial growth and nodulation, but there is currently little available information on the potential inhibitory effects. Therefore, common seed fungicidal and insecticidal treatments were assessed to determine adverse impacts on rhizobial inoculants both in vitro, on treated seed, and in the field. METHODS AND RESULTS: Initially, the in vitro toxicity of the seed-applied fungicides Thiram 600, P-Pickel T (PPT), their active ingredients (thiram and thiabendazole) and the insecticide Gaucho to rhizobia was measured with filter discs containing varying concentrations of the pesticides. Pea and chickpea seed was then coated with the same pesticides and inoculated with rhizobia in different inoculant substrates to determine bacterial survival and nodulation. Finally, a field trial using the fungicide PPT and commercial inoculants was conducted. Some seed fungicide treatments were found to be inhibitory to rhizobia and reduce nodulation under monoxenic conditions and in the field. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide more detailed information on the compatibility of specific rhizobial inoculants with common seed-applied pesticides. This research will provide information on the compatibility of rhizobia and seed-applied pesticides, and assist farmers to select sowing practices which reduce the risk of crop nodulation failures.

Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome.

OBJECTIVES: To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). METHODS: This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. RESULTS: Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). CONCLUSIONS: HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.

[An epidemiologic study of pelvic organ prolapse in urban Chinese women: a population-based sample in China].

Objective: This study aimed to assess the prevalence and factors associated with pelvic organ prolapse (POP) in a representative sample of Chinese urban women. Methods: A total of 29613 Chinese urban women were recruited to this cross-sectional study between February 2014 and March 2016. The prevalence of POP, defined as any stage Ⅱ or higher POP resulting in symptoms, was assessed using questionnaires and physical examinations. Multivariable logistic regression was used to assess factors associated with POP. Results: 2 864 of 29 613 women (9.67%) had POP. The prevalence of POP increased with age ranging from 1.23% (82/6 646) of women aged between 20 and 29 years to 26.11% (727/2 784) for those aged 70 years or older (P<0.000 1). Overweight and obese women were more likely to have POP than normal weight women [AOR=1.56, 95%CI 1.42-1.72 vs AOR=1.74, 95%CI 1.48-2.03]. In the multivariate analysis, the independent risk factors were cough (AOR=1.70, 95%CI 1.44-2.02), constipation (AOR=2.05, 95%CI 1.82-2.32), physical disease (AOR=1.27, 95%CI 1.15-1.41), and gynecological diseases (AOR=2.08, 95%CI 1.89-2.29). Nulliparous (AOR=0.12, 95%CI 0.06-0.22) and caesarean section (CS) (AOR=0.55, 95%CI 0.47-0.64) were protective factors for POP. Conclusions: POP affects nearly 10% of women in Chinese urban region. The prevalence of POP increases significantly with age. The independent risk factors for POP are body mass index, cough, constipation, physical disease and gynecological diseases. Nulliparous and CS are protective factors for POP.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

Magnetic anisotropy manipulation of the femtosecond laser-excited spin wave modes in full-Heusler Co2Fe1-x Mn x Al films.

Spin-wave dynamics in full-Heusler Co2Fe1-x Mn x Al films have been investigated using all-optical pump-probe magneto-optical polar Kerr spectroscopy. We find magnetic damping and anisotropy can be modulated by composition x. Damon-Eshbach (DE) spin wave occurs only in the samples which present intrinsic magnetic damping and have huge uniaxial magnetic anisotropy, implying that intrinsic magnetic damping and huge uniaxial magnetic anisotropy is the necessary conditions to excite coherent DE spin wave. Kittel spin wave appears in low uniaxial magnetic anisotropic samples and presents extrinsic magnetic damping. Therefore, laser-excited spin-wave modes can be manipulated by magnetic anisotropy, whose physical picture is discussed phenomenologically.