bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normalization weighted combination scores re-evaluate TNM staging of gastric cancer: a retrospective cohort study based on a multicenter database
Authors: Wu Junpeng , Wang Hao , Yin Xin , Wang Yufei , Lu Zhanfei , Zhang Jiaqi , Zhang Yao , Xue Yingwei 
Published: November 2023

Background:
The pathological depth of tumor invasion (pT) and lymph node metastasis (pN) are critical independent prognostic factors for patients with gastric cancer, representing effective methods for evaluating prognosis. In this study, we employed a normalization weight combination score to calculate the weight ratio of the pT stage and pN stage. Subsequently, we established a novel wTN staging model based on these T and N weights, evaluating its prognostic capacity.

Methods:
This study utilized a training cohort from A Medical University Cancer Hospital and a validation cohort from the SEER database. LASSO and Cox regression were employed to screen clinical characteristics. Multivariate linear regression and cluster analysis calculated the weight ratio of T stage and N stage in the training and validation cohorts, respectively, followed by re-staging. Prognostic value was evaluated using C-index, likelihood ratio, Wald, and Score tests for wTN stage and TNM stage. A nomogram model was developed, and accuracy was assessed using ROC, DCA, and RCS analyses.

Results:
LASSO was used for initial screening, selecting 8 potential features for Cox analysis. Age, tumor size, MLNs, and tumor location were confirmed as independent prognostic factors. wTN was calculated in the training and validation cohorts, and nomograms were established with the independent factors. N stage had a higher weight proportion than T stage in both cohorts (0.625/0.375 in training cohort, 0.556/0.444 in validation cohort). wTN outperformed the 8th TNM stage in C-index, likelihood ratio, Wald, and Score tests in the training cohort, with successful validation in the validation cohort. Stratified analysis of distinct pathological types further demonstrates that wTN staging exhibits superior prognostic performance.

Conclusion:
The wTN staging model based on T stage and N stage weights has a good prognostic value for gastric cancer patients. The same conclusion was obtained in different pathological stratification.
Six steps for a successful aesthetic free flap reconstruction shaping after minimally invasive mastectomy – a retrospective case-control study
Authors: Wong Allen Wei-Jiat , Kuo Wen-Ling , Cheong David Chon-Fok , Tsai Hsiu-Pei , Kao Shu-Wei , Chen Chia-Fang , Huang Jung-Ju 
Published: November 2023

Objective:Breast cancer treatment has evolved to the modern skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM). To better perform these surgeries, minimally invasive techniques using the endoscope, or Da Vinci Robotic Surgery platform have been developed. The deep inferior epigastric perforator (DIEP) flap is the gold standard in breast reconstruction, but it is still not commonly performed after minimally invasive mastectomy due technical difficulty. Here we introduced six key steps to a successful aesthetic autologous free flap reconstruction in in minimally invasive mastectomies.Methods:There are six main steps to our technique: placement of mastectomy incision, precise flap design after angiography studies, trial of shaping, transcutaneous medial suture, footprint recreation and post-operative shaping with bra. Between November 2018 and July 2022, a total of 67 immediate breast reconstructions using free perforator flaps were performed in 63 patients after minimally invasive NSM.Results:The results from the minimally invasive mastectomy group were compared with a group of conventional mastectomy patients (n=41) performed during the same period. There were no significant differences in flap exploration rates. 100% of the flaps survived. In the minimally invasive group, the final scar was placed in the lateral region, where it would be hidden from the anterior view. Only 70.7% of the conventional mastectomy group could achieve a hidden lateral scar (P<0.001). The aesthetic revision rates were similar between two groups.Conclusion:With attention to the six steps above, autologous free flap reconstruction can be offered reliably in the setting of minimally invasive mastectomy.
Benefit of perioperative radiotherapy for hepatocellular carcinoma: a quality-based systematic review and meta-analysis
Authors: Rim Chai Hong , Park Sunmin , Yoon Won Sup 
Published: November 2023

Introduction:
Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative treatment has been established, the authors performed a meta-analysis to evaluate the benefits of perioperative radiotherapy (RT).

Methods:
The PubMed, MEDLINE, EMBASE, and Cochrane Library were searched until May 2023. Randomized or propensity-matched studies evaluating at least five major clinical factors investigating benefit of perioperative RT, were included. The main effect measure were the pooled odds ratios (OR) regarding the benefit of perioperative RT using 2-year overall survival (OS) and 1-year disease-free survival (DFS) data.

Results:
Seven studies (five randomized and two propensity-matched studies) involving 815 patients were included. The pooled ORs for 1-year DFS and 2-year OS were 0.359 (95% CI: 0.246–0.523) and 0.371 (95% CI: 0.293–0.576), respectively, favoring perioperative RT, with very low heterogeneity. In the subgroup analyses, the benefits of OS and DFS were consistent between the two subgroups [portal vein thrombosis (PVT) and narrow resection margin (RM) groups]. In the PVT subgroup, the pooled OS rates at both 1-year and 2-year (75.6 vs. 36.9%, P<0.001; 25.6 vs. 9.9%, P=0.004) and DFS rates at both 1-year and 2-year (25.2 vs. 10.3%, P=0.194; 11.9 vs. 3.0%, P=0.022) were higher in the perioperative RT group. In the narrow RM subgroup, the surgery and RT groups showed higher pooled OS rates for both 1-year and 2-year (97.3 vs. 91.9%, P=0.042; 90.4 vs. 78.7%, P=0.051) and DFS (88.1 vs. 72.6%, P<0.001; 70.1 vs. 51.7%, P<0.001). Grade 5 toxicity was not reported, and three studies reported grade ≥3 or higher liver function test abnormalities, ranging from 4.8–19.2%.

Conclusion:
The present study supports the oncological benefits of perioperative RT, for cases with high-risk of recurrence. Oncologic outcomes between subgroups differed according to clinical indications.
Amino acid kinetics in the critically ill
Authors: Deutz Nicolaas E.P. , Haines Krista L. , Wischmeier Paul E. , Engelen Mariëlle P.K.J. 
Published: November 2023

Purpose of review
Stable isotope methods have been used for many years to assess whole body protein and amino acid kinetics in critically ill patients. In recent years, new isotope approaches and tracer insights have been developed. The tracer pulse approach has some advantages above the established primed-continuous tracer infusion approach because of the high amount of metabolic information obtained, easy applicability, and low tracer costs. Effects of disease severity and sex on amino acid kinetics in ICU patients will also be addressed.

Recent findings
Current knowledge was synthesized on specific perturbations in amino acid metabolism in critically ill patients, employing novel methodologies such as the pulse tracer approach and computational modeling. Variations were evaluated in amino acid production and linked to severity of critical illness, as measured by SOFA score, and sex. Production of the branched-chain amino acids (BCAAs), glutamine, tau-methylhistidine and hydroxyproline were elevated in critical illness, likely related to increased transamination of the individual BCAAs or increased breakdown of proteins. Citrulline production was reduced, indicative of impaired gut mucosa function. Sex and disease severity independently influenced amino acid kinetics in ICU patients.

Summary
Novel tracer and computational approaches have been developed to simultaneously measure postabsorptive kinetics of multiple amino acids that can be used in critical illness. The collective findings lay the groundwork for targeted individualized nutritional strategies in ICU settings aimed at enhancing patient outcomes taking into account disease severity and sex.
The future of HOXA-expressing leukemias: Menin inhibitor response and resistance
Authors: Wenge Daniela V. , Armstrong Scott A. 
Published: November 2023

Purpose of review
We provide an update on the successes and ongoing challenges of Menin inhibition as a novel approach for the treatment of patients with acute leukemias that express HOXA cluster genes including leukemias with KMT2A-rearrangements, NPM1 mutations or NUP98-rearrangements. Initial clinical trials show promising response rates in heavily pretreated patients suggesting these inhibitors may have a significant impact on patient outcome. Furthermore, the development of resistance mutations that decrease drug binding affinity, validates Menin as a therapeutic target in human cancers. Therapeutic strategies aiming at overcoming and preventing resistance, are of high clinical relevance.

Recent findings
Several Menin inhibitor chemotypes have entered clinical trials. Acquired point mutations have recently been described as a mechanism of resistance towards Menin inhibitors. However, resistance can develop in absence of these mutations. Combination therapies are currently being investigated in preclinical models and in early phase clinical trials.

Summary
Given the remarkable overall response rates, shedding light on treatment options for patients whose leukemias develop resistance to Menin inhibitors is an imminent clinical need. Studying the underlying mechanisms to inform clinical decision making, and to potentially prevent the development of resistance is of outmost importance.
Obstructive sleep apnea for the rhinologist
Authors: Nogues Juan C. , Jain Nikhita , Chou Courtney T. , Lin Fred Y. 
Published: November 2023

Purpose
Obstructive sleep apnea (OSA) is a ubiquitous disease defined by repetitive partial or complete cessation of airflow during sleep caused by upper airway collapse. Otolaryngologists play a crucial role in the management of OSA, which is rapidly evolving with the advent of new surgical techniques and medical devices. Here we review the medical and surgical treatment options for OSA with a focus on unique considerations for patients with OSA who undergo nasal, sinus, and skull base surgery.

Recent findings
Treatment of OSA includes both nonsurgical and surgical options. Positive airway pressure (PAP) therapy remains the first-line medical treatment for OSA, but alternatives such as oral appliance and positional therapy are viable alternatives. Surgical treatments include pharyngeal and tongue base surgery, hypoglossal nerve stimulation therapy, and skeletal surgery. Nasal surgery has been shown to improve sleep quality and continuous positive airway pressure (CPAP) tolerance and usage. Sinus and skull base patients with comorbid OSA have special perioperative considerations for the rhinologist to consider such as the need for overnight observation and timing of CPAP therapy resumption.

Summary
OSA patients present with special considerations for the rhinologist. Patients with moderate to severe OSA may benefit from overnight observation after ambulatory surgery, especially those with an elevated BMI, cardiopulmonary comorbidities, and those who are not using CPAP regularly at home. Though CPAP may be safely resumed in the perioperative setting of nasal, sinus, and skull base surgery, the exact timing depends on patient, surgeon, and systemic factors such as severity of OSA, CPAP pressures required, extent of surgery, and the postoperative monitoring setting. Lastly, nasal and sinus surgery can improve sleep quality and CPAP tolerance and compliance in patients with OSA.
Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System
Authors: Makunts Tigran , Joulfayan Haroutyun , Abagyan Ruben 
Published: November 2023

AbstractGlucagon receptor-like peptide receptor agonists, GLP-1 RAs, are one of the most commonly used drugs for type-2 diabetes mellitus. The clinical guidelines recommend GLP-1 RAs as adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, obesity, and other cardiometabolic conditions. The weight loss seen in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled black boxed warning of the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of most recent postmarketing safety data is warranted to quantify thyroid hyperplasia and neoplasms instances. In this study we analyzed over eighteen million reports from United States Food and Drug Administration Adverse Event Reporting System and identified 17,653 relevant GLP-1 RA monotherapy reports to provide the evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA as monotherapy when compared to patients taking sodium-glucose cotransporter-2 inhibitor monotherapy.
Re-emergence of Sylvatic Dengue 2 during an outbreak in Southeastern Senegal, Kedougou 2020
Authors: Dieng Idrissa , Diarra Maryam , Sadio Bacary Djilocalisse , Gaye Alioune , Sow Bocar , Dior Ndione Marie Henriette , Diallo Diawo , Ndiaye Mignane , Diallo Amadou , Sankhe Safietou , Faye Martin , Diop Boly , Sall Amadou Alpha , Fall Gamou , Faye Oumar , Loucoubar Cheikh , Faye Ousmane , Weaver Scott C. , Diallo Mawlouth , Barry Mamadou Aliou , Diagne Moussa Moise 
Published: November 2023

AbstractDengue outbreaks in West Africa, linked to urban cycle viruses, pose a significant public health threat. In 2020, a sylvatic Dengue 2 outbreak in Kedougou, southeastern Senegal, resulted in 59 confirmed cases, suggesting these strains may not require additional adaptation but could re-emerge into urban transmission cycles in the region.
Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease
Authors: Curtis David 
Published: November 2023

AbstractAn important issue pertinent to the analysis of sequence data to detect association between rare variants in a gene and a given phenotype is the ability to annotate nonsynonymous variants in terms of their likely importance as affecting protein function. While a number of software tools attempt to do this, AlphaMissense was recently released and was shown to have good performance using benchmarks based on variants causing severe disease and on functional assays. Here, we assess the performance of AlphaMissense across 18 genes which had previously demonstrated association between rare coding variants and hyperlipidaemia, hypertension or type 2 diabetes. Ability to detect association, expressed as the signed log p value (SLP) was compared between AlphaMissense and 43 other annotation methods. The results demonstrated marked variability between genes regarding the extent to which nonsynonymous variants contributed to evidence for association and also between the performance of different methods of annotating the nonsynonymous variants. Although AlphaMissense produced the highest SLP on average across genes, it produced the maximum SLP for only 4 genes. For some genes, other methods produced a considerably higher SLP and there were examples of genes where AlphaMissense produced no evidence for association while another method performed well. The marked inconsistency across genes means that it is difficult to decide on an optimal method of analysis of sequence data. The fact that different methods perform well for different genes suggests that if one wished to use sequence data for individual risk prediction then gene-specific annotation methods should be used. It would be desirable to have the ability to recognise characteristics of a gene which could facilitate the selection of an annotation method which would best discriminate variants of interest within that gene.This research has been conducted using the UK Biobank Resource.
Threat of shock increases distractor susceptibility during the short-term maintenance of visual information
Authors: Casalvera Abigail , Goodwin Madeline , Lynch Kevin , Teferi Marta , Patel Milan , Grillon Christian , Ernst Monique , Balderston Nicholas L 
Published: November 2023

AbstractBACKGROUNDWork on anxiety related attention control deficits suggests that elevated arousal impacts the ability to filter out distractors. To test this, we designed a task to look at distractor suppression during periods of threat. We administered trials of a visual short-term memory (VSTM) task, during periods of unpredictable threat, and hypothesized that threat would impair performance during trials where subjects were required to filter out large numbers of distractors.METHODExperiment 1 involved fifteen healthy participants who completed one study visit. They performed four runs of a VSTM task comprising 32 trials each. Participants were presented with an arrow indicating left or right, followed by an array of squares. They were instructed to remember the target side and disregard the distractors on the off-target side. A subsequent target square was shown, and participants indicated whether it matched one of the previously presented target squares. The trial conditions included 50% matches and 50% mismatches, with an equal distribution of left and right targets. The number of target and distractor squares varied systematically, with high (4 squares) and low (2 squares) target and distractor conditions. Trials alternated between periods of safety and threat, with startle responses recorded using electromyography (EMG) following white noise presentations.Experiment 2 involved twenty-seven healthy participants who completed the same VSTM task inside an MRI scanner during a single study visit. The procedure mirrored that of Experiment 1, except for the absence of white noise presentations.RESULTSFor Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. However, results suggested that the white noise probes interfered with performance. For Experiment 2, we found that both accuracy was affected by threat, such that distractor load negatively impacted accuracy only in the threat condition.CONCLUSIONOverall, these findings suggest that threat affects distractor susceptibility during the short-term maintenance of visual information. The presence of threat makes it more difficult to filter out distracting information. We believe that this is related to hyperarousal of parietal cortex, which has been observed during unpredictable threat.
Low Positive Social Determinants of Health Exposure Amplifies the Association between Allostatic Load and Risk of Cardiovascular Mortality in Cancer and Non-Cancer Patients
Authors: Bhave Aditya , Reddy Ritu , Moore Justin X. , Nain Priyanshu , Datta Biplab , Nettles Darryl , Seth Lakshya , Jiang Stephanie , Patel Vraj , Malik Sarah , Weintraub Neal , Al-Kindi Sadeer G , Ganatra Sarju , Dani Sourbha , Gomez-Valencia Javier , Wang Xiaoling , Guha Avirup 
Published: November 2023

AbstractBackgroundHigh allostatic load (AL) is associated with an increased risk of cardiovascular death (CVD), but little is known about how social determinants moderate this relationship.MethodsWe conducted a retrospective cohort analysis of the National Health and Nutrition Examination Survey years 1999-2010 linked with the National Death Index. We fit age, race, and sex-adjusted Fine & Gray models to calculate sub-distribution hazard ratios (SHR) of CVD among adults exposed to high versus low levels of positive social determinants of health (PSDOH), stratified by high and low AL status.ResultsAmong 22,775 participants, 1,939 (8.5%) had a cancer history. In the full cohort, low PSDOH was associated with 38% increased risk of CVD among high AL adults (SHR: 1.38, 95% CI: 1.22 - 1.56) and 57% increased risk among low AL adults (SHR: 1.57, 95% CI: 1.32 - 1.87). Among adults with no cancer history, low PSDOH was associated with 36% increased risk among high AL adults (SHR: 1.36, 95% CI: 1.19 – 1.55) and 59% increased risk among low AL adults (SHR: 1.59, 95% CI: 1.32 – 1.92). In the cancer cohort, low PSDOH was associated with 77% increased risk among high AL adults (SHR: 1.77, 95% CI: 1.32 – 2.37) and 73% increased risk among low AL adults (SHR: 1.73, 95% CI: 1.02 – 2.94).ConclusionsLow PSDOH amplified the association between AL and CVD in all cohorts, with the highest risk increases among adults with cancer history. This suggests that socioeconomic-related distress supersedes biological changes from AL in relation to CVD.
The Clinimetric Profile of 11 Generic Quality Indicators for Appropriate Antibiotic Use in Hospitalized Patients in Indonesia
Authors: Tunjungputri Rahajeng N. , Lie Khie Chen , Susilo Adityo , Nainggolan Freddy C. , Jasirwan Chyntia O.M. , Hidayat Rudy , Purnamasari Dyah , Sinto Robert , Nelwan Erni J. 
Published: November 2023

ABSTRACTBackgroundOne of the efforts in antibiotic stewardship for limiting antibiotic resistance is the assessment of the quality of antibiotic use. To date, the quality and appropriateness of antibiotic use in Indonesia, a low-middle-income non-European country, have not yet been assessed using proven quality indicators (QIs). One recommended tool to measure appropriate empiric antibiotic use in hospitalized patients is the generic QIs reported by van den Boschet. al., which demonstrated good validity and generalizability.ObjectiveThe aim of this study is to assess the clinimetric profile of 11 generic QIs based on van den Boschet. al. in admitted adult patients receiving empiric antibiotics in Indonesian hospitals.MethodsThis is an observational study with a cross-sectional design conducted at two government referral hospitals in Jakarta, Indonesia, from August 1, 2022, to February 2, 2023. Adult inpatients who received empiric antibiotics due to suspected infection for ≥24 hours were included in the study.ResultsIn 500 inpatients from 2 hospitals, all QIs demonstrated good measurability with less than 10% of missing data. Ten QIs showed good applicability of >10%. Four QIs show good performance, while six QIs have significant potential for improvement (two blood cultures are obtained before empiric antibiotic treatment; culture sample is obtained from location suspected of infection; antibiotic is switched from intravenous to oral when clinically possible; antibiotics are stopped when there is no evidence of infection; a guideline is available and renewed every three years; and a guideline is adjusted to the local resistance pattern) making them priority targets for interventions to enhance the quality of antibiotic use in Indonesia. All QIs display good inter-observer reliability, and no moderate or strong correlations are found between QIs.ConclusionThe clinimetric assessment of QIs is imperative before their implementation in any setting different from their country of origin. Of the 11 generic QIs, 10 demonstrated good reliability and applicability at two hospitals in Indonesia. Future intervention studies can utilize these generic QIs to measure improvement in the appropriateness of antibiotic use.