Identification and characterization of a potential strain for the production of polyhydroxyalkanoate from glycerol.

While poly (3-hydroxybutyrate) (PHB) holds promise as a bioplastic, its commercial utilization has been hampered by the high cost of raw materials. However, glycerol emerges as a viable feedstock for PHB production, offering a sustainable production approach and substantial cost reduction potential. Glycerol stands out as a promising feedstock for PHB production, offering a pathway toward sustainable manufacturing and considerable cost savings. The identification and characterization of strains capable of converting glycerol into PHB represent a pivotal strategy in advancing PHB production research. In this study, we isolated a strain, Ralstonia sp. RRA (RRA). The strain exhibits remarkable proficiency in synthesizing PHB from glycerol. With glycerol as the carbon source, RRA achieved a specific growth rate of 0.19 h-1, attaining a PHB content of approximately 50% within 30 h. Through third-generation genome and transcriptome sequencing, we elucidated the genome composition and identified a total of eight genes (glpR, glpD, glpS, glpT, glpP, glpQ, glpV, and glpK) involved in the glycerol metabolism pathway. Leveraging these findings, the strain RRA demonstrates significant promise in producing PHB from low-cost renewable carbon sources.

Chemotherapy Rechallenge or Reintroduction Compared to Regorafenib or Trifluridine/Tipiracil for Pretreated Metastatic Colorectal Cancer Patients: A Propensity Score Analysis of Treatment Beyond Second Line (Proserpyna Study).

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated. PATIENTS AND METHODS: PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses. RESULTS: Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses. CONCLUSIONS: Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.

Height matters: An EEG study of the relative height disadvantage promoting third-party punishment.

The study employed event-related potential (ERP), time-frequency analysis, and functional connectivity to comprehensively explore the influence of male's relative height on third-party punishment (TPP) and its underlying neural mechanism. The results found that punishment rate and more transfer amount are significantly greater when the height of the third-party is lower than that of the recipient, suggesting that male's height disadvantage promotes TPP. Neural results found that the height disadvantage induced a smaller N1. The height disadvantage also evoked greater P300 amplitude, more theta power, and more alpha power. Furthermore, a significantly stronger wPLI between the rTPJ and the posterior parietal and a significantly stronger wPLI between the DLPFC and the posterior parietal were observed when third-party was at the height disadvantage. These results imply that the height disadvantage causes negative emotions and affects the fairness consideration in the early processing stage; The third-party evaluates the blame of violators and makes an appropriate punishment decision later. Our findings indicate that anger and reputation concern caused by height disadvantage promote TPP. The current study holds significance as it underscores the psychological importance of height in males, broadens the perspective on factors influencing TPP, validates the promoting effect of personal disadvantages on prosocial behavior, enriches our understanding of indirect reciprocity theory, and extends the application of the evolution theory of Napoleon complex.

Development and external validation of Indian population-specific Garbhini-GA2 model for estimating gestational age in second and third trimesters.

Background: A large proportion of pregnant women in lower and middle-income countries (LMIC) seek their first antenatal care after 14 weeks of gestation. While the last menstrual period (LMP) is still the most prevalent method of determining gestational age (GA), ultrasound-based foetal biometry is considered more accurate in the second and third trimesters. In LMIC settings, the Hadlock formula, originally developed using data from a small Caucasian population, is widely used for estimating GA and foetal weight worldwide as the pre-programmed formula in ultrasound machines. This approach can lead to inaccuracies when estimating GA in a diverse population. Therefore, this study aimed to develop a population-specific model for estimating GA in the late trimesters that was as accurate as the GA estimation in the first trimester, using data from GARBH-Ini, a pregnancy cohort in a North Indian district hospital, and subsequently validate the model in an independent cohort in South India. Methods: Data obtained by longitudinal ultrasonography across all trimesters of pregnancy was used to develop and validate GA models for the second and third trimesters. The gold standard for GA estimation in the first trimester was determined using ultrasonography. The Garbhini-GA2, a polynomial regression model, was developed using the genetic algorithm-based method, showcasing the best performance among the models considered. This model incorporated three of the five routinely measured ultrasonographic parameters during the second and third trimesters. To assess its performance, the Garbhini-GA2 model was compared against the Hadlock and INTERGROWTH-21st models using both the TEST set (N = 1493) from the GARBH-Ini cohort and an independent VALIDATION dataset (N = 948) from the Christian Medical College (CMC), Vellore cohort. Evaluation metrics, including root-mean-squared error, bias, and preterm birth (PTB) rates, were utilised to comprehensively assess the model's accuracy and reliability. Findings: With first trimester GA dating as the baseline, Garbhini-GA2 reduced the GA estimation median error by more than three times compared to the Hadlock formula. Further, the PTB rate estimated using Garbhini-GA2 was more accurate when compared to the INTERGROWTH-21st and Hadlock formulae, which overestimated the rate by 22.47% and 58.91%, respectively. Interpretation: The Garbhini-GA2 is the first late-trimester GA estimation model to be developed and validated using Indian population data. Its higher accuracy in GA estimation, comparable to GA estimation in the first trimester and PTB classification, underscores the significance of deploying population-specific GA formulae to enhance antenatal care. Funding: The GARBH-Ini cohort study was funded by the Department of Biotechnology, Government of India (BT/PR9983/MED/97/194/2013). The ultrasound repository was partly supported by the Grand Challenges India-All Children Thriving Program, Biotechnology Industry Research Assistance Council, Department of Biotechnology, Government of India (BIRAC/GCI/0115/03/14-ACT). The research reported in this publication was made possible by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC. The external validation study at CMC Vellore was partly supported by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC and by Exploratory Research Grant (SB/20-21/0602/BT/RBCX/008481) from Robert Bosch Centre for Data Science and Artificial Intelligence (RBCDSAI), IIT Madras. An alum endowment from Prakash Arunachalam (BIO/18-19/304/ALUM/KARH) partly funded this study at the Centre for Integrative Biology and Systems Medicine, IIT Madras.

3DMOUSEneST: a volumetric, label-free imaging method evaluating embryo-uterine interaction and decidualization efficacy.

Effective interplay between the uterus and the embryo is essential for pregnancy establishment, however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extraembryonic tissues) growth. We demonstrate that decidual nest volume is a measurable indicator of decidualization efficacy and correlates with the probability of early pregnancy progression based on a logistic regression analysis using Smad1/5 and Smad2/3 conditional knockout mice with known implantation defects. 3DMOUSEneST has great potential to become a principal method for studying decidual fibrillar collagen and characterizing mouse models associated with early embryonic lethality and fertility issues.

Ultrafast Laser Manipulation of In-Lattice Plasmonic Nanoparticles.

Plasmonic nanoparticles enable manipulation and enhancement of light fields at deep subwavelength scales, leading to structures and devices for diverse applications in optics. Despite hybrid plasmonic materials display remarkable optical properties due to interactions between components in nanoproximity, scalable production of plasmonic nanostructures within a single-crystalline matrix to achieve an ideal plasmon-crystal interface remains challenging. Here, a novel approach is presented to realize efficient manipulation of in-lattice plasmonic nanoparticles. Employing ultrafast-laser-driven plasmonic nanolithography, metallic nanoparticles with controllable morphology are precisely defined in the crystalline lattice of yttrium aluminum garnet (YAG) crystal. Through direct ion implantation, hybrid plasmonic material composed of nanoparticles embedded in a sub-surface amorphous YAG layer is created. Subsequently, femtosecond laser pulses guide formation and reshaping of plasmonic nanoparticles from the amorphous layer into the single-crystalline matrix along direction of light propagation, facilitated by a plasmon-mediated evolution of laser energy deposition. By tailoring resonance modes and optimizing the coupling between structured particle assemblies, a range of applications including polarization-dependent absorption and nonlinearity, controllable photoluminescence, and structural color generation is demonstrated. This research introduces a new approach for fabricating advanced optical materials featuring in-lattice plasmonic nanostructures, paving the way for the development of diverse functional photonic devices.

Comparison of the Cameriere's third molar maturity index and Olze et al.'s stages of radiographic visibility of the root pulp in a Turkish population.

Purpose: The purpose of this study was to compare the Cameriere's third molar maturity index and Olze et al.'s stages of radiographic visibility of the root pulp in estimating the age of maturity in the Turkish population. The age of majority, which is legally significant, marks the transition from childhood to adulthood. In Turkey, the age of majority is set at 18 years. As the third molars continue to develop at this age, they can serve as an indicator of dental age. Materials and methods: A total of 705 panoramic radiographs obtained from individuals aged 15 to 22 years, including children and adults, were included in this study. The left mandibular third molars were evaluated on panoramic radiographs using Cameriere's third molar maturity index and Olze's method of radiographic root pulp visibility (RPV) stages. Minimum and maximum values were noted for each stage, and a median with upper and lower quartiles, as well as mean and standard deviation were calculated. Sensitivity and specificity values were calculated. Results: In males, Cameriere's third molar maturity index demonstrated a sensitivity of 0.77% and specificity of 0.96%, while in females, it showed a sensitivity of 0.57% and specificity of 0.92%. Regarding Olze et al.'s stage 0, the sensitivity and specificity values were 0.86% and 0.79% in males, and 0.85% and 0.75% in females, respectively. Conclusion: Although both methods can be used to distinguish individuals below or above the age of 18, the cut-off value suggested by Cameriere's method resulted in a higher rate of type 2 error (false negativity). Therefore, the method proposed by Olze et al., based on the radiographic visibility of the root pulp, can be employed to differentiate between adults and minors in the Turkish population.

Fasting blood glucose as a screening measure for late-onset gestational diabetes in the third trimester.

OBJECTIVE: To investigate the positive rate of late-onset gestational diabetes mellitus (GDM) by additional fasting blood glucose (FBG) screening at 32-34 gestational weeks (GW) and analyse the perinatal outcomes of late-onset GDM after standard treatment. DESIGN: An Prospective cohort study. SETTING: Single centre in China. POPULATION: 1130 singleton pregnancies with negative GDM screening in their first and second trimester. METHODS: Additional FBG testing was performed at 32-34 GW. Pregnancies with FBG ≥5.1 mmol/L were diagnosed as GDM and received standardized treatment. Perinatal outcomes were collected and compared. MAIN OUTCOME MEASURES: Diagnosis of late-onset GDM, obstetric and neonatal outcomes. RESULTS: 6.3% (71/1130) of participants had FBG values ≥5.1 mmol/L and were diagnosed with late-onset GDM. Sixty-five (91.5%) were treated by dietary therapy and 6 (8.5%) by insulin therapy. The perinatal outcomes of full-term delivery were compared. The incidence of macrosomia (22.7% vs. 5.1%, adjusted odds ratio (aOR) 5.51, 95% confidence interval (CI) 1.83-16.61, p = 0.002) and NICU transferring (18.3% vs. 10.1%, aOR 1.94, 95% CI 1.01-3.74, p = 0.046) was significantly higher in late-onset GDM group than that in FBG <5.1 mmol/L group. Elevated FBG was associated with overweight or obesity during pregnancy (54.9% vs. 34.9%, OR 2.27, 95% CI 1.40-3.68, p = 0.001). CONCLUSIONS: 6.3% of singleton pregnancies with normal GDM screening results in the first and second trimester were found to have late-onset GDM by additional FBG screening at 32-34 GW, and their risk of macrosomia during a full-term pregnancy remains significantly higher after standard treatment.

Retrospective analysis of the effects of impacted third molar on hematologic patients undergoing hematopoietic stem cell transplantation.

Objective: This study aimed to investigate the incidence, treatment status, and impact position of impacted third molars (ITM) and their effects on patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A retrospective analysis was conducted on the medical records of 454 patients who underwent HSCT, out of which 188 patients had ITM. The presence of ITM and its association with transplant-related infections and complications were recorded and analyzed. Results: Patients with ITM were significantly younger. The number of mandibular ITM was notably higher than maxillary ones, and the risk of pericoronitis in mandibular ITM was significantly higher than in maxillary ones. Out of 311 ITM in 188 patients, 25 were extracted before transplantation. The proportion of extraction and treatment for ITM with pericoronitis or caries was significantly higher than that for ITM without such problems. Moreover, patients with a history of pre-transplant pericoronitis had a significantly higher probability of developing tooth-related complications during transplantation, caused by pericoronitis in ITM compared to patients without a history of pericoronitis. Conclusion: Pre-transplant examination and treatment of ITM are essential, especially in cases with a history of pericoronitis. Oral intervention can significantly reduce the occurrence of tooth-related complications related to ITM during transplantation.

Morphological examination of the visual system and orbital region in the red panda (Ailurus fulgens fulgens).

OBJECTIVES: The red panda is currently the only surviving member of the Ailuridae family in the Caniformia suborder. In this study, we provide data on anatomical, morphometric, histological and histochemical examination of the orbital region, eyelids, orbital gland, and eye tunics in two adult males Ailurus fulgens fulgens from the Wroclaw Zoological Garden, Poland. METHODS: The study involved morphometric analysis of the eyeball and selected accessory organs of the eye, along with analysis of the bony orbit, including its morphometry, macroscopic, and microscopic evaluation. Microscopic evaluation encompassed histological and histochemical staining, with the former involving hematoxylin & eosin (H&E), Movat pentachrome, picro-Mallory trichrome, Fontana-Masson, and the latter including PAS, AB pH 1.0, AB pH 2.5; AB pH 2.5/PAS, and HDI. RESULTS: The upper (UE) and lower (LE) eyelids presented well-developed tarsal glands, sebaceous glands, and a characteristic simple alveolar gland (producing a mucous secretion). The palpebral part of the lacrimal gland was present. A single lymphoid follicle was observed only in the upper eyelids. The superficial gland of the third eyelid (SGTE) was a multilobar acinar complex that produces mucous secretion and is contained within the interlobular ducts of numerous aggregates of lymph nodes. The third eyelid (TE) was T-shaped and composed of hyaline tissue, containing CALT. The lacrimal gland (LG) also revealed a multilobar acinar complex that produced mucous secretion, with a single lymphoid follicle. The cornea consisted of 4 layers, as Bowman's membrane was absent. The Vogt palisades composed of 7-10 layers of epithelial cells were demonstrated. The pupil was horizontally ovoid at rest (post-mortem). The sphincter pupil and the dilator pupil were well developed. Macroscopically, the tapetum lucidum appeared as a milky, non-opalescent crescent. Histologically, the choroidal tapetum lucidum cellulosum consisted of 5 to 9 layers of loosely packed oval cells. The retina showed a composition similar to that of terrestrial nocturnal carnivores. CONCLUSIONS: The results of our research indicate that the anatomical features of the eye and orbital region in the red panda share similarities with those described in the Musteloidea clade, as well as the Canidae and Ursidae families.

Effect of impacted mandibular third molar extraction on periodontal microbiota and clinical parameters of adjacent teeth: A randomized clinical trial.

It is urgently necessary to clarify the effect of extraction of impacted mandibular third molar (IMTM) on the periodontal tissue of adjacent second molars (ASMs). In this study, the ASM periodontal condition and pathogenic microbes were assessed before IMTM extraction and at 1, 4, 8 and 12 weeks postoperatively. Based on the inclusion and exclusion criteria, our study revealed that IMTM extractions adversely affected distal － periodontal probing depth (dPPD), attachment loss (dAL), plaque index (dPLI) and bleeding on probing (dBOP) within 8 weeks, but these indices gradually normalize after 12 weeks. The subgingival pathogens near the ASMs distal surface, Porphyromonas and Pseudomonas, were significantly increased postoperatively. Moreover, relevance of ASMs clinical indices and subgingival microbes after IMTM extractions was found. In contrast to the situation in chronic periodontitis, the effects of IMTM extraction on dPPD, dAL, dPLI and dBOP of ASMs were mainly correlated with Pseudomonas. Additionally, while the IMTM extractions have adverse distal periodontal indices of ASMs within 8 weeks and increase subgingival pathogens, the modified triangular flap (MTF) had fewer distal periodontal indices and less Pseudomonas. Compared to the traditional envelope flap and triangular flap, the MTF benefits the periodontal health, which could be considered as the priority option for IMTM extractions.

Effect of platelet-rich fibrin on the recovery after third molar surgery: A systematic review and meta-analysis.

This meta-analysis aimed to elucidate the effects of platelet-rich fibrin (PRF) on the recovery of alveolar bone after surgical removal of the mandibular third molars. PubMed, Cochrane Library, Web of Science, and Embase databases were searched from the inception to February 2023 for relevant studies on the application of PRF after the extraction of impacted mandibular third molars, with the language limited to English. Literature screening was conducted by two independent researchers. The Cochrane risk-of-bias tool was adopted for quality evaluation, and Stata 15.0 was used for statistical analysis. A total of 33 randomized controlled trials were included in the present study. Following surgical removal of the mandibular third molars, 1139 tooth sockets were filled with PRF, while 1138 sockets were sutured after conventional saline irrigation. The meta-analyses showed that PRF can relieve pain [(RR 0.454; 95% CI 0.23, 0.891); (SMD -0.74; 95% CI -0.97, 0.52)], improve swelling (SMD -1.48; 95% CI -1.90, -1.06), alleviate trismus (SMD -0.35; 95% CI -0.51, -0.19), reduce dry socket (SMD -0.18; 95% CI -030, -0.05), and promote bone tissue healing (SMD 2.34; 95% CI 0.18, 4.51). The current study confirms that PRF can reduce some postoperative complications. Local application of PRF after lower third molar extraction is a viable method for relieving pain and swelling, reducing the incidence of dry socket and trismus, and increasing bone density. However, whether it can promote soft tissue healing remains unclear. For patients undergoing complicated surgical extraction, local application of PRF into the sockets might be a good option.

Is there evidence for the(sole) use of third ventriculostomy in the treatment of Idiopathic. Intracranial Hypertension: A Literature Review.

BACKGROUND: Idiopathic intracranial hypertension (IIH) remains a poorly understood condition with no standardised treatment. Treatment is therefore generally individualised. Recent isolated reports have begun to describe the use of third ventriculostomy (open or closed) for the treatment of IIH. This review aims to communicate the current evidence for the use of third ventriculostomy in IIH. METHODS: A systemic review, using PubMed, was performed of studies describing the use of third ventriculostomy, either open or closed, for the treatment of idiopathic intracranial hypertension. RESULTS: Only 3 studies for a total of 3 patients were found in which a third ventriculostomy was performed for the treatment of IIH. CONCLUSION: Despite very plausible proposed mechanisms of action, there is currently a paucity of both studies and, therefore, evidence for the use of either endoscopic or open third ventriculostomy for the treatment of IIH. The studies done to date do strongly suggest that further consideration is warranted.

Accuracy of second and third molar maturity indices, Olze, Haavikko, and Demirjian methods for 14- and 16-year-old age thresholds assessment in Croatian children and adolescents.

This study explores the reliability of four established legal age threshold estimation approaches in a Croatian sample. We applied Haavikko stages, Demirjian stages, Olze's third molar eruption stages, and second and third molar maturity indices measurement in 593 orthopantomograms of Croatian children and adolescents aged 11.00-20.99 years old. The left mandibular second and third molar were assessed. Logistic regression analysis was conducted to test the significance of predictive variables. Logistic Receiver operating characteristic (ROC) curves were performed to evaluate the classification ability of variables for estimating 14- and 16-year-old thresholds. The areas under the ROC curve (AUC), accuracy (Acc), sensitivity (Se), specificity (Sp), Positive Likelihood Ratio (LR +), Negative Likelihood Ratio (LR-), and Bayes post-test probability (Bayes PTP) were calculated to evaluate classification performance. Results suggest that the combination of I2M&I3M is the best classifier for the 14-year-old threshold (AUC = 0.879); for males alone, I2M is an even better classifier (AUC = 0.881). The highest Acc 80.1% (95%CI, 75.9%-83.9%), Bayes PTP 86.5% (95%CI, 82.8%-89.7%) and Sp 88.9% (95%CI, 83.0%-93.3%) were by I3M < 0.81 & I2M < 0.03 in total samples; the highest Acc 86.1% (80.6%- 90.6%), Bayes PTP 87.2% (95%CI, 81.7%- 91.4%) and Sp 87.8% (95%CI, 78.2%- 94.3%) were by I2M < 0.01 in males, Acc of Haavikko Ac and Demirjian H stage in second molar is very close with slightly lower Bayes PTP and Sp. I3M is a good classifier for 16-year-old threshold (AUC = 0.889). The cut-off value I3M < 0.34 can be used to classify the 16-year-old threshold with Acc of 80.6% (95%CI, 77.2%-83.7%), Sp of 83.4% (95%CI, 79.0%-87.3%), and 81.7% (95%CI, 78.4%-84.8%) Bayes PTP. In conclusion, to classify the 14-year-old threshold, a pair of cut-off values I3M < 0.81 & I2M < 0.03 can be used in Croatian females; I2M < 0.01, Demirjian H stage, Haavikko Ac stage in second molar, and the pair I3M < 0.81 & I2M < 0.03 can all be used in Croatian males. I3M < 0.34 can classify the 16-year-old threshold in Croatian populations.

The efficacy of almonertinib and anlotinib combination therapy for advanced non-small-cell lung cancer patients who continued to experience cancer progression during third-generation EGFR-TKI treatment: a retrospective study.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are key drivers in a significant portion of non-small-cell lung cancer (NSCLC) patients. While third-generation EGFR-tyrosine kinase inhibitors (TKIs) such as osimertinib have demonstrated efficacy, the management of patients who continue to experience disease progression during treatment remains challenging. The emergence of drug resistance, including the development of secondary mutations, necessitates exploration of alternative treatment strategies. This study aims to evaluate and observe the efficacy and safety of almonertinib combined with anlotinib in patients after cancer progression during third-generation EGFR-TKI therapy. METHODS: In this retrospective analysis, we included EGFR-mutated NSCLC patients who were resistant to third-generation EGFR-TKIs. All patients were treated with almonertinib combined with anlotinib. The clinical characteristics, treatment history, clinical benefits, and adverse events of these patients were retrospectively collected. RESULTS: A total of 16 eligible patients were included in the analysis. The results revealed that combination therapy with almonertinib and anlotinib was effective in this patient cohort. The overall response rate was 25% and the disease control rate was 93.75%. The 6 and 12 months of PFS rates were 92.9% (95% confidence interval [CI] 80.3%, 100.0%) and 84.4% (95% CI 66.6%, 100.0%), respectively. Moreover, this combination therapy was generally well-tolerated, with manageable adverse events. CONCLUSION: Our retrospective analysis suggests that almonertinib and anlotinib combination therapy may represent a viable option for EGFR-mutated NSCLC patients who have progressed on third-generation EGFR-TKIs, especially for those with posterior lines and no standard treatment options. Further investigation and larger clinical trials are warranted to validate these observations and refine treatment guidelines.

Normal Pregnancy Care and Physiology and Select Pregnancy Complications: A Flipped Classroom Case for the OB/GYN Clerkship.

Introduction: This module teaches core knowledge and skills for undergraduate medical education in reproductive health, providing instruction in the management of normal and abnormal pregnancy and labor utilizing interactive small-group flipped classroom methods and case-based instruction. Methods: Advance preparation materials were provided before the education session. The 2-hour session was facilitated by clinical educators using a faculty guide. Using voluntary surveys, we collected data to measure satisfaction among obstetrics and gynecology clerkship students and facilitators following each education session. Results: Capturing six clerkships spanning 9 months, 116 students participated, and 64 students completed the satisfaction survey, with 97% agreeing that the session was helpful in applying knowledge and principles to common clinical scenarios. Most students (96%) self-reported that they achieved the session's learning objectives utilizing prework and interactive small-group teaching. Nine clinical instructors completed the survey; all agreed the provided materials allowed them to facilitate active learning, and the majority (89%) agreed they spent less time preparing to teach this curriculum compared to traditional didactics. Discussion: This interactive flipped classroom session meets clerkship learning objectives related to the management of pregnancy and labor using standardized materials. The curriculum reduced preparation time for clinical educators as well.

Correlation of amniotic fluid inflammatory markers with preterm birth: a meta-analysis.

BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.

Comprehensive and deep evaluation of structural variation detection pipelines with third-generation sequencing data.

BACKGROUND: Structural variation (SV) detection methods using third-generation sequencing data are widely employed, yet accurately detecting SVs remains challenging. Different methods often yield inconsistent results for certain SV types, complicating tool selection and revealing biases in detection. RESULTS: This study comprehensively evaluates 53 SV detection pipelines using simulated and real data from PacBio (CLR: Continuous Long Read, CCS: Circular Consensus Sequencing) and Nanopore (ONT) platforms. We assess their performance in detecting various sizes and types of SVs, breakpoint biases, and genotyping accuracy with various sequencing depths. Notably, pipelines such as Minimap2-cuteSV2, NGMLR-SVIM, PBMM2-pbsv, Winnowmap-Sniffles2, and Winnowmap-SVision exhibit comparatively higher recall and precision. Our findings also show that combining multiple pipelines with the same aligner, like pbmm2 or winnowmap, can significantly enhance performance. The individual pipelines' detailed ranking and performance metrics can be viewed in a dynamic table: http://pmglab.top/SVPipelinesRanking . CONCLUSIONS: This study comprehensively characterizes the strengths and weaknesses of numerous pipelines, providing valuable insights that can improve SV detection in third-generation sequencing data and inform SV annotation and function prediction.

Purely Endoscopic Supracerebellar Infratentorial Approach to the Pineal Region in Pediatric Population.

Pineal lesions represent less than 1% of all brain tumors (Villani et al., Clin Neurol Neurosurg 109:1-6, 2007). The abysmal location and critical neurovascular structures remain a surgical challenge, despite the advent of microneurosurgery. The classical wide surgical suboccipital craniotomy with the supracerebellar infratentorial approach, described by Sir Victor Horsley (Victor, Proc R Soc Med 3:77-78, 1910), is infamous for its considerable surgical morbidity and mortality. This was later upgraded microneurosurgically by Stein to improve surgical outcomes (Stein, J Neurosurg 35:197-202, 1971).Ruge et al. reported the first purely endoscopic fenestration of quadrigeminal arachnoid cysts via this corridor (Ruge et al., Neurosurgery 38:830-7, 1996). A cadaver-based anatomical study by Cardia et al. demonstrated the viability for endoscope-assisted techniques (Cardia et al., J Neurosurg 2006;104(6 Suppl):409-14). However, the first purely endoscopic supracerebellar infratentorial (eSCIT) approach to a pineal cyst was performed in 2008 by Gore et al. (Gore PA et al., Neurosurgery 62:108-9, 2008).Unlike transventricular endoscopy, eSCIT approach poses no mechanical risk to the fornices and can be utilized irrespective of ventricular size. More vascular control and resultant reduction in uncontrolled hemorrhage improve the feasibility of attaining complete resection, especially around corners (Zaidi et al,, World Neurosurg 84, 2015). Gravity-dependent positioning and cerebrospinal fluid (CSF) diversion aid cerebellar relaxation, creating the ideal anatomical pathway. Also, angle of the straight sinus, tentorium, and tectal adherence can often influence the choice of approach; thus direct endoscopic visualization not only counteracts access to the engorged Galenic complex but also encourages sharp dissection of the arachnoid (Cardia et al., J Neurosurg 104:409-14, 2006). These tactics help provide excellent illumination with magnification, making it less fatiguing for the surgeon (Broggi et al., Neurosurgery 67:159-65, 2010).The purely endoscopic approach thwarts the dreaded risk of air embolisms, via simple copious irrigation from a small burr hole (Shahinian and Ra, J Neurol Surg B Skull Base 74:114-7, 2013). The tiny opening and closure are rapid to create, and the smaller wound decreases postoperative pain and morbidity. Recent literature supports its numerous advantages and favorable outcomes, making it a tough contender to traditional open methods.

How people are exposed to neighborhoods racially different from their own.

In US cities, neighborhoods have long been racially segregated. However, people do not spend all their time in their neighborhoods, and the consequences of residential segregation may be tempered by the contact people have with other racial groups as they traverse the city daily. We examine the extent to which people's regular travel throughout the city is to places "beyond their comfort zone" (BCZ), i.e., to neighborhoods of racial composition different from their own-and why. Based on travel patterns observed in more than 7.2 million devices in the 100 largest US cities, we find that the average trip is to a neighborhood less than half as racially different from the home neighborhood as it could have been given the city. Travel to grocery stores is least likely to be BCZ; travel to gyms and parks, most likely; however, differences are greatest across cities. For the first ~10 km people travel from home, neighborhoods become increasingly more BCZ for every km traveled; beyond that point, whether neighborhoods do so depends strongly on the city. Patterns are substantively similar before and after COVID-19. Our findings suggest that policies encouraging more 15-min travel-that is, to amenities closer to the home-may inadvertently discourage BCZ movement. In addition, promoting use of certain "third places" such as restaurants, bars, and gyms, may help temper the effects of residential segregation, though how much it might do so depends on city-specific conditions.