bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and validation of biomarkers of immune cell-related genes in postmenopausal osteoporosis: An observational study
Authors: Chen Lihua , Zhao Yu , Qiu Jingjing , Lin Xiaosheng
Published: May 2024

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.
Osseoscopy-assisted core decompression and debridement in the treatment of avascular necrosis of the femoral head
Authors: Mutlu Müren , Zora Hakan , Bayrak Gökhan , Bilgen Ömer Faruk
Published: May 2024

Core decompression of the femoral head is a standard surgical procedure used in the early stages of the femoral head avascular necrosis (AVN) (Steinberg I to III). This study aimed to determine whether the advantages of osseoscopy-assisted core decompression using a standard arthroscopic set up in the early stages of AVN of the femoral head. Twelve hips of 12 patients who underwent osseoscopy-assisted core decompression and debridement with the diagnosis of AVN of the femoral head were reviewed between 2019 and 2021. The etiology was idiopathic in 2 patients; ten had a history of steroid use. The preoperative and postoperative first month Harris Hip Score (HHS) and visual analogue scale (VAS) were recorded. Standard X-rays, computerized tomography, and magnetic resonance imaging (MRI) were noted at preoperatively and sixth month follow-ups. In a 1-year follow-up, X-rays and MRIs were reviewed. All patients significantly improved in the VAS and HHS after the osseoscopy-assisted core decompression (P = .002). Two of the 12 patients with an initial stage of Steinberg IIC and IIB and one with Steinberg IA had a progressive femoral collapse and, therefore, had a total hip replacement at the end of the follow-up. Nine patients (75%) had satisfactory functional and radiological results in 1-year of follow-up. However, 3 patients (25%) culminated in total hip arthroplasty in a 1-year follow-up. Using an arthroscopic set up during osseoscopy-assisted core decompression surgery of the femoral head AVN has the benefits of direct visualization and accurate debridement of the involved area. The osseoscopy-assisted core decompression technique avoids excessive debridement of the healthy bone tissue adjacent to the necrotic area.
Mechanisms of microbiota modulation: Implications for health, disease, and therapeutic interventions
Authors: Ugwu Okechukwu Paul-Chima , Alum Esther Ugo , Okon Michael Ben , Obeagu Emmanuel I.
Published: May 2024

Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.
Exploring the efficacy and molecular mechanism of Danhong injection comprehensively in the treatment of idiopathic pulmonary fibrosis by combining meta-analysis, network pharmacology, and molecular docking methods
Authors: Wu Xiaozheng , Li Wen , Luo Zhenliang , Chen Yunzhi
Published: May 2024

Background:

Danhong injection, a compound injection of Chinese herbal medicine, has been widely used in idiopathic pulmonary fibrosis (IPF) at present as an adjuvant treatment. However, the clinical efficacy and molecular mechanism of IPF are still unclear. This study will evaluate and explore the clinical efficacy and molecular mechanism of Danhong injection in the treatment of IPF.

Methods:

In meta-analysis, the computer was used to search 8 databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, CNKI, WanFang, and VIP) to collect the RCTs, and RevMan 5.3 and Stata 14.0 were used for statistical analysis. It has been registered on PROSPERO: CRD42020221096. In network pharmacology, the main chemical components and targets of the chemical components of Danhong injection were obtained in TCMSP and Swiss Target Prediction databases. The main targets of IPF were obtained through Gencards, Disgenet, OMIM, TTD, and DRUGBANK databases. The String platform was used to construct PPI networks. Cytoscape 3.8.2 was used to construct the “Danhong components – IPF targets-pathways” network. The molecular docking verification was conducted by Auto Dock.

Results:

Twelve RCTs were finally included with a total of 896 patients. The meta-analysis showed that Danhong injection could improve the clinical efficiency ([OR] = 0.25, 95% CI [0.15, 0.41]), lung function, arterial blood gas analysis, inflammatory cytokines, and serum cytokines associated with pulmonary fibrosis of IPF patients, respectively (P < .05). The core active components of Danhong injection on IPF were Luteolin, Quercetin, and Kaempferol, and the core targets were PTGS2, AR, ESR1, PPARG, and RELA. Danhong injection mainly improved IPF through PD-L1 expression and PD-1 checkpoint path in cancer, pathways in cancer, PI3K-Akt signaling pathway, etc.

Conclusion:

These results provided scientific basis for the clinical use of Danhong injection for the treatment of IPF, and provided a new direction to explore the potential mechanism of action of Danhong injection.
Brain structure comparison among Parkinson disease, essential tremor, and healthy controls using 7T MRI
Authors: Moon Hyeong Cheol , Kim Aryun , Park Young Seok
Published: May 2024

Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often present with similar initial symptoms, making their differentiation challenging with magnetic resonance imaging (MRI) techniques. This study aimed to identify structural brain differences among PD, ET, and health controls (HCs) using 7-Tesla (T) MRI. We assessed the whole-brain parcellation in gray matter volume, thickness, subcortical volume, and small regions of basal ganglia in PD (n = 18), ET (n = 15), and HCs (n = 18), who were matched for age and sex. Brain structure analysis was performed automatic segmentation through Freesurfer software. Small regions of basal ganglia were manually segmented by ITK-SNAP. Additionally, we examined the associations between clinical indicators (symptom duration, unified Parkinson diseases rating scale (UPDRS), and clinical rating scale for tremor (CRST)) and brain structure. PD showed a significant reduction in gray matter volume in the postcentral region compared to ET. ET showed a significant reduction in cerebellum volume compared to HCs. There was a negative correlation between CRST scores (B and C) and gray matter thickness in right superior frontal in ET. This study demonstrated potential of 7T MRI in differentiating brain structure differences among PD, ET, and HCs. Specific findings, such as parietal lobe atrophy in PD compared to ET and cerebellum atrophy in ET compared to HCs, the importance of advanced imaging techniques in accurately diagnosing and distinguishing between movement disorders that present with similar initial symptoms.
Identification and validation of a prognostic anoikis-related gene signature in papillary thyroid carcinoma by integrated analysis of single-cell and bulk RNA-sequencing
Authors: Zheng Ke , Zhang Xiu-Xia , Yu Xin , Yu Bin , Yang Yi-Fei
Published: May 2024

Papillary thyroid carcinoma (PTC) prognosis may be deteriorated due to the metastases, and anoikis palys an essential role in the tumor metastasis. However, the potential effect of anoikis-related genes on the prognosis of PTC was unclear. The mRNA and clinical information were obtained from the cancer genome atlas database. Hub genes were identified and risk model was constructed using Cox regression analysis. Kaplan–Meier (K–M) curve was applied for the survival analysis. Immune infiltration and immune therapy response were calculated using CIBERSORT and TIDE. The identification of cell types and cell interaction was performed by Seurat, SingleR and CellChat packages. GO, KEGG, and GSVA were applied for the enrichment analysis. Protein-protein interaction network was constructed in STRING and Cytoscape. Drug sensitivity was assessed in GSCA. Based on bulk RNA data, we identified 4 anoikis-related risk signatures, which were oncogenes, and constructed a risk model. The enrichment analysis found high risk group was enriched in some immune-related pathways. High risk group had higher infiltration of Tregs, higher TIDE score and lower levels of monocytes and CD8 T cells. Based on scRNA data, we found that 4 hub genes were mainly expressed in monocytes and macrophages, and they interacted with T cells. Hub genes were significantly related to immune escape-related genes. Drug sensitivity analysis suggested that cyclin dependent kinase inhibitor 2A may be a better chemotherapy target. We constructed a risk model which could effectively and steadily predict the prognosis of PTC. We inferred that the immune escape may be involved in the development of PTC.
Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review
Authors: Wang Xujie , Zhang Huan , Li Long , Fu Jixin , Wang Xinjian
Published: May 2024

Rationale:

Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes.

Patient concerns:

Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again.

Diagnoses:

CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands.

Interventions:

After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively.

Outcomes:

Five months after the surgery, the patient died due to brain metastasis.

Lessons:

The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.
Performance Analysis of Leica Biosystems Monoclonal Antibody Programmed Cell Death Ligand 1 Clone 73-10 on Breast, Colorectal, and Hepatocellular Carcinomas
Authors: Shilo Konstantin , Shen Tiansheng , Hammond Scott , Parwani Anil V. , Li Zaibo , Dayal Shubham , Chiweshe Joseph , Lian Fangru
Published: May 2024

Programmed cell death receptor 1/Programmed cell death ligand 1 (PD-L1) checkpoint pathway is responsible for the control of immune cell responses. Immunotherapy using checkpoint inhibitors, such as anti–PD-L1 therapy, aids disease management and potentiates clinical outcomes. This study aimed to analyze the performance of the Leica Biosystems (LBS) USA FDA class I in vitro diagnostic monoclonal antibody (clone 73-10) to detect PD-L1 expression in breast, colorectal, and hepatocellular carcinomas compared with the class III FDA-approved PD-L1 detecting antibodies [SP263 (Ventana), 22C3 (Dako), and 28-8 (Dako)] using 208 unique tissue microarray–based cases for each tumor type. The interassay concordances between LBS 73-10 clone and other PD-L1 antibodies ranged from 0.59 to 0.95 Cohen kappa coefficient (K) and from 0.66 to 0.90 (K) for cutoff values of 1% and 50% tumor proportion score (TPS), respectively. The 73-10 clones showed inter-pathologist agreements ranging from 0.53 to 1.0 (K) and 0.34 to 0.94 (K) for cutoff values of 1% and 50% TPS, respectively. For the immune cell proportion score (IPS) using a cutoff of 1%, the Kappa coefficient of interassay concordances and inter-pathologist agreements ranged from 0.34 to 0.94. The 73-10 clone assay’s sensitivity ranged from 78.3% to 100% (TPS ≥1%), 100% (TPS ≥50%), and 77.4% to 93.5% (IPS ≥1%), while its specificity was 97.9% to 100% (TPS ≥1%), 99.5% to 99.8% (TPS ≥50%), and 97.9% to 100% (IPS ≥1%). This exploratory evaluation of LBS 73-10 monoclonal antibody on a large set of breast, colorectal, and hepatocellular carcinomas showed the assay’s technical performance is comparable to the FDA-approved companion/complementary diagnostics PD-L1 detection assays.
Associations of Patient and Parent Characteristics With Parental Decision Regret in the PICU: A Secondary Analysis of the 2015–2017 Navigate Randomized Comparative Trial*
Authors: Ashworth Rachel C. , Malone Jay R. , Franklin Dana , Sorce Lauren R. , Clayman Marla L. , Frader Joel , White Douglas B. , Michelson Kelly N.
Published: May 2024

OBJECTIVES:

To identify self-reported meaningful decisions made by parents in the PICU and to determine patient and parent characteristics associated with the development of parental decision regret, a measurable, self-reported outcome associated with psychologic morbidity.

DESIGN:

Secondary analysis of the Navigate randomized comparative trial (NCT02333396).

SETTING:

Two tertiary, academic PICUs.

PATIENTS:

Spanish- or English-speaking parents of PICU patients aged less than 18 years who were expected to remain in the PICU for greater than 24 hours from time of enrollment or who had a risk of mortality greater than 4% based on Pediatric Index of Mortality 2 score.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Between April 2015 and March 2017, 233 parents of 209 patients completed a survey 3–5 weeks post-PICU discharge which included the Decision Regret Scale (DRS), a 5-item, 5-point Likert scale tool scored from 0 (no regret) to 100 (maximum regret). Two hundred nine patient/parent dyads were analyzed. The decisions parents reported as most important were categorized as: procedure, respiratory support, medical management, parent–staff interactions and communication, symptom management, fluid/electrolytes/nutrition, and no decision. Fifty-one percent of parents had some decision regret (DRS > 0) with 19% scoring in the moderate–severe range (DRS 26–100). The mean DRS score was 12.7 (sd18.1). Multivariable analysis showed that parental Hispanic ethnicity was associated with greater odds ratio (OR 3.12 [95% CI, 1.36–7.13];p= 0.007) of mild regret. Being parents of a patient with an increased PICU length of stay (LOS) or underlying respiratory disease was associated with greater odds of moderate–severe regret (OR 1.03 [95% CI, 1.009–1.049];p= 0.004 and OR 2.91 [95% CI, 1.22–6.94];p= 0.02, respectively).

CONCLUSIONS:

Decision regret was experienced by half of PICU parents in the 2015–2017 Navigate study. The characteristics associated with decision regret (parental ethnicity, PICU LOS, and respiratory disease) are easily identifiable. Further study is needed to understand what contributes to regret in this population and what interventions could provide support and minimize the development of regret.
Brief Report: Evaluating the Efficacy of Psychobehavioral Interventions for Cardiovascular Risk Among People Living With HIV: A Systematic Review and Meta-Synthesis of Randomized Controlled Trials
Authors: Foley Jacklyn D. , Bernier Lauren B. , Ngo Long , Batchelder Abigail W. , O'Cleirigh Conall , Lydston Melissa , Yeh Gloria
Published: May 2024

People with HIV (PWH) are disproportionately affected by cardiovascular disease (CVD). Psychobehavioral therapies are capable of targeting the pathophysiology underlying HIV-CVD comorbidity. This study synthesized findings from randomized controlled trials of psychobehavioral therapies for reducing CVD risk among PWH following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were as follows: (1) used a randomized controlled trial design, (2) evaluated a cognitive–behavioral or mindfulness-based therapy, (3) sampled adults (age ≥18 years) with HIV, (4) measured a behavioral (eg, diet) or biological (eg, immune functioning) CVD risk factor, and (5) published in an English-language peer-reviewed journal. Electronic searches were conducted in 6 databases (eg, MEDLINE) using controlled vocabulary and free-text synonyms for HIV, psychobehavioral therapy, and CVD risk. Data were independently extracted with consensus reached. Outcomes were immune activation, tobacco smoking, stress, inflammation, and physical activity from 33 studies. There were stronger effects for psychobehavioral interventions compared with controls on CD4 [Hedge g = 0.262, 95% confidence interval (CI) = 0.127 to 0.396] and tobacco-smoking abstinence (Hedge g = 0.537, 95% CI = 0.215 to 0.86). There were no differences or insufficient data for stress, inflammation, or physical activity. No eligible studies examined psychobehavioral interventions on blood pressure, lipids, or weight in PWH. There is increasing importance to further invest in broader CVD risk reduction effort for PWH that include psychobehavioral intervention strategies.
Amputated Digit Replantations
Authors: Fijany Arman J. , Chaker Sara C. , Egozi Hannah P. , Hung Ya-Ching , Hill Bradford J. , Bhandari Laxminarayan , Thayer Wesley P. , Lineaweaver William C.
Published: May 2024

Introduction

A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates.

Methods

The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval.

Results

Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0–12 hours of warm ischemia time (P ≤ 0.05). The odds of survival in the early (0–6 hours) replantation group were around 40% greater than the later (6–12 hours) replantation group (P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers (P ≤ 0.05).

Discussion

Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.
Nasopharyngoscopic Evaluation of Velopharyngeal Closure During Speech
Authors: Slavin Blaire V. , Mirsky Nicholas A. , Paolucci Nicholas M. , Nayak Vasudev Vivekanand , T. Younis Ramzi , Coelho Paulo G. , Thaller Seth R.
Published: May 2024

Definitive oronasal separation through closure of the velopharyngeal (VP) sphincter is necessary for the development of normal speech and feeding. Individuals with velopharyngeal incompetence or insufficiency often exhibit hypernasal speech, poor speech intelligibility, and nasal regurgitation. Assessment of VP sphincter function using nasopharyngoscopy is a key element in identifying VP dysfunction. A foundational understanding of normal anatomy and physiology of the velopharyngeal mechanism is paramount to successful diagnosis. This includes recognition of 4 distinct VP sphincter closure patterns: coronal, sagittal, circular, and circular with Passavant’s ridge. In this study, the authors showcase 2 patients with velopharyngeal competence who presented to an ear, nose, and throat clinic for nasopharyngoscopic evaluation. This study sought to demonstrate the use of nasopharyngoscopy to recognize velopharyngeal closure patterns and discuss how they may influence the surgical management of VP dysfunction.
Dehiscence and Fistula Formation Following Anterior Palatal Reconstruction With Vomer Flap
Authors: Menville Jesse E. , Spake Carole , Soliman Luke , Shinde Nidhi , Persad-Paisley Elijah M. , Baranwal Navya , Woo Albert S.
Published: May 2024

Background and Purpose:

Anterior palatal reconstruction using vomer flaps has been described during primary cleft lip repair. In this procedure, the mucoperiosteal tissue of the vomer is elevated to reconstruct the nasal mucosa overlying the cleft of the hard palate. Here the authors, evaluate the efficacy of a technique in which a superiorly based vomer flap is sutured to the lateral nasal mucosa. The authors assess vomer flap dehiscence rates and compare the likelihood of fistula development in this cohort to patients who underwent palatoplasty without vomer flap reconstruction.

Methods:

A retrospective chart review was conducted of all palatoplasties performed by the senior author at an academic institution during a 7-year period. Medical records were reviewed for demographic variables, operative characteristics, and postoperative complications up to 1 year following surgery. Logistic regression analysis was conducted to assess the effects of vomer flap reconstruction on fistula formation, adjusting for age and sex.

Results:

Fifty-eight (N=58) patients met the inclusion criteria. Of these, 38 patients (control group) underwent cleft palate reconstruction without previous vomer flap placement. The remaining 20 patients underwent cleft lip repair with vomer flap reconstruction before palatoplasty (vomer flap group). When bilateral cases were counted independently, 25 total vomer flap reconstructions were performed. Seventeen of these 25 vomer flap reconstructions (68%) were completely dehisced by the time of cleft palate repair. In the vomer flap group, 3 of the 20 patients (15%) developed fistulas in the anterior hard palate following the subsequent palatoplasty procedure. In the control group, only 1 of the 38 patients (2.6%) developed a fistula in the anterior hard palate. There was no significant association between cohorts and the development of anterior hard palate fistulas [odds ratio=10.88, 95% confidence interval (0.99–297.77) P=0.07], although analysis was limited by low statistical power due to the small sample size.

Conclusions:

In our patient population, anterior palatal reconstruction using a superiorly based vomer flap technique was associated with complete dehiscence in 68% of cases. Fistula formation in the anterior hard palate was also proportionately higher following initial vomer flap reconstruction (15% versus 2.6%). These results prompted the senior author to adjust his surgical technique to 1 in which the vomer flap overlaps the oral mucosa. While follow-up from these adjusted vomer flap reconstruction cases remains ongoing, early evidence suggests a reduced requirement for surgical revision following implementation of the modified technique.
Predicting Mortality Prior to Interhospital Hospital for “Unseen” General Surgery Patients
Authors: Al-deen Said Sayf , Gentle Corey K. , Gross Abby , Nimylowycz Kelly , Hossain Mir Shanaz , Weathers Allison , Walsh R. Matthew , Steele Scott R. , Regueiro Miguel , Augustin Toms
Published: May 2024

Objective:

Develop and validate a mortality risk calculator that could be utilized at the time of transfer, leveraging routinely collected variables that could be obtained by trained non-clinical transfer personnel.

Summary Background Data:

There are no objective tools to predict mortality at the time of inter-hospital transfer for Emergency General Surgery (EGS) patients that are “unseen” by the accepting system.

Methods:

Patients transferred to general or colorectal surgery services from January 2016 through August 2022 were retrospectively identified and randomly divided into training and validation cohorts (3:1 ratio). The primary outcome was admission-related mortality, defined as death during the index admission or within 30 days post-discharge. Multiple predictive models were developed and validated.

Results:

Among 4,664 transferred patients, 280 (6.0%) experienced mortality. Predictive models were generated utilizing 19 routinely collected variables; the penalized regression model was selected over other models due to excellent performance using only 12 variables. The model performance on the validating set resulted in an area under the receiver operating characteristic curve, sensitivity, specificity, and balanced accuracy of 0.851, 0.90, 0.67, and 0.79, respectively. After bias correction, Brier score was 0.04, indicating a strong association between the assigned risk and the observed frequency of mortality.

Conclusion:

A risk calculator using twelve variables has excellent predictive ability for mortality at the time of interhospital transfer among “unseen” EGS patients. Quantifying a patient’s mortality risk at the time of transfer could improve patient triage, bed and resource allocation, and standardize care.
A New Functional Threshold for Minimally Invasive Lobectomy
Authors: Vanstraelen Stijn , Tan Kay See , Dycoco Joe , Adusumilli Prasad S. , Bains Manjit S. , Bott Matthew J. , Downey Robert J. , Gray Katherine D. , Huang James , Isbell James M. , Molena Daniela , Park Bernard J. , Rusch Valerie W. , Sihag Smita , Jones David R. , Rocco Gaetano
Published: May 2024

Objective:

To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy.

Background:

Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment.

Methods:

All patients who underwent MIS lobectomy for clinical stage I to II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry and colleagues' study.

Results:

In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified [79% (95% CI, 76%–81%) vs 65% (95% CI, 62%–68%); P<0.001]. The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45% to 60% and >60% was prolonged air leak [33 (13%) vs 34 (6%); P<0.001]. The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values.

Conclusions:

The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.
A narrative review of community-based dementia care in India: experiences, challenges, and policy initiatives
Authors: Thomas Trisha , Dasgupta Jayashree
Published: May 2024

Purpose of review

India is facing a significant increase in the aging population who are at risk for dementia. This review evaluates recent literature on community-based care, focusing on caregiver experiences, challenges and policy initiatives.

Recent findings

Dementia care in India is traditionally provided by family members who take on the role of caregivers. Studies on caregiver experiences have reflected high caregiving burden and related impact on their mental health. During the pandemic, caregivers experienced several unprecedented challenges in providing care, emphasizing the need for more research on community-based dementia care across the country. Telehealth and online caregiver training were identified as viable alternatives to support community dementia care. However, it may not be a feasible mode of delivery suitable across the Indian context, underscoring the need for culturally relevant and acceptable interventions. India is currently undertaking concerted policy efforts for dementia care through multiple initiatives like the National Program for Healthcare of the Elderly, the Mental Healthcare Act, and initiatives like the Atal Vayo Abhyuday Yojna. These initiatives aim to address the healthcare requirements of the elderly; nevertheless, a comprehensive evaluation of their impact is yet to be discerned.

There is a need for comprehensive research, to inform evidence-based policy and improve dementia care systems in India. Addressing gaps in existing dementia care capacities and healthcare initiatives, along with tailoring interventions to India's diverse contexts are critical for effective community care for dementia
Opioid vaccine clinical testing: lessons learned
Authors: Luba Rachel , Comer Sandra D.
Published: May 2024

Purpose of review

Opioid use disorder (OUD) presents a serious public health concern, with dramatic increases in opioid-overdose mortality in recent years and a small percentage of those with OUD accessing or remaining engaged with available treatments. Efforts are currently underway to identify vaccines targeting opioids, which could provide a novel and complimentary approach. The current review provides an overview of existing literature, practical considerations for designing and conducting clinical trials with vaccines for opioids, and future directions.

Recent findings

This review covers the following themes: clinical trial design and selection of endpoints, timepoint selection, practical considerations and lessons learned from the first (ongoing) trial of a vaccine targeting opioids, and future directions.

Efforts to develop and test vaccines targeting OUD are based on a foundation of preclinical work and close collaboration between preclinical and clinical researchers. Efforts to learn from shortcomings of prior clinical trials of vaccines for other substances are essential in designing and testing effective vaccines for OUD. Design and implementation of clinical trials for a vaccine for OUD requires careful balance of participant safety and strategies for retention and efforts to gather viable data to inform future work.
Automated Cytometric Gating with Human-Level Performance Using Bivariate Segmentation
Authors: Chen Jiong , Ionita Matei , Feng Yanbo , Lu Yinfeng , Orzechowski Patryk , Garai Sumita , Hassinger Kenneth , Bao Jingxuan , Wen Junhao , Duong-Tran Duy , Wagenaar Joost , McKeague Michelle L. , Painter Mark M. , Mathew Divij , Pattekar Ajinkya , Meyer Nuala J. , John Wherry E. , Greenplate Allison R. , Shen Li
Published: May 2024

Recent advances in cytometry technology have enabled high-throughput data collection with multiple single-cell protein expression measurements. The significant biological and technical variance between samples in cytometry has long posed a formidable challenge during the gating process, especially for the initial gates which deal with unpredictable events, such as debris and technical artifacts. Even with the same experimental machine and protocol, the target population, as well as the cell population that needs to be excluded, may vary across different measurements. To address this challenge and mitigate the labor-intensive manual gating process, we propose a deep learning framework UNITO to rigorously identify the hierarchical cytometric subpopulations. The UNITO framework transformed a cell-level classification task into an image-based semantic segmentation problem. For reproducibility purposes, the framework was applied to three independent cohorts and successfully detected initial gates that were required to identify single cellular events as well as subsequent cell gates. We validated the UNITO framework by comparing its results with previous automated methods and the consensus of at least four experienced immunologists. UNITO outperformed existing automated methods and differed from human consensus by no more than each individual human. Most critically, UNITO framework functions as a fully automated pipeline after training and does not require human hints or prior knowledge. Unlike existing multi-channel classification or clustering pipelines, UNITO can reproduce a similar contour compared to manual gating for each intermediate gating to achieve better interpretability and provide post hoc visual inspection. Beyond acting as a pioneering framework that uses image segmentation to do auto-gating, UNITO gives a fast and interpretable way to assign the cell subtype membership, and the speed of UNITO will not be impacted by the number of cells from each sample. The pre-gating and gating inference takes approximately 2 minutes for each sample using our pre-defined 9 gates system, and it can also adapt to any sequential prediction with different configurations.
Improving polygenic prediction from summary data by learning patterns of effect sharing across multiple phenotypes
Authors: Kunkel Deborah , Sørensen Peter , Shankar Vijay , Morgante Fabio
Published: May 2024

Polygenic prediction of complex trait phenotypes has become important in human genetics, especially in the context of precision medicine. Recently, Morganteet al. introducedmr.mash, a flexible and computationally efficient method that models multiple phenotypes jointly and leverages sharing of effects across such phenotypes to improve prediction accuracy. However, a drawback ofmr.mashis that it requires individual-level data, which are often not publicly available. In this work, we introducemr.mash-rss, an extension of themr.mashmodel that requires only summary statistics from Genome-Wide Association Studies (GWAS) and linkage disequilibrium (LD) estimates from a reference panel. By using summary data, we achieve the twin goal of increasing the applicability of themr.mashmodel to data sets that are not publicly available and making it scalable to biobank-size data. Through simulations, we show thatmr.mash-rssis competitive with, and often outperforms, current state-of-the-art methods for single- and multi-phenotype polygenic prediction in a variety of scenarios that differ in the pattern of effect sharing across phenotypes, the number of phenotypes, the number of causal variants, and the genomic heritability. We also present a real data analysis of 16 blood cell phenotypes in UK Biobank, showing thatmr.mash-rssachieves higher prediction accuracy than competing methods for the majority of traits, especially when the data has smaller sample size.

Author summary

Polygenic prediction refers to the use of an individual’s genetic information (i.e., genotypes) to predict traits (i.e., phenotypes), which are often of medical relevance. It is known that some phenotypes are related and are affected by the same genotypes. When this is the case, it is possible to improve the accuracy of predictions by using methods that model multiple phenotypes jointly and account for shared effects.mr.mashis a recently developed multi-phenotype method that can learn which effects are shared and has been shown to improve prediction. However,mr.mashrequires large data sets of genetic and phenotypic information collected at the individual level. Such data are often unavailable due to privacy concerns, or are difficult to work with due to the computational resources needed to analyze data of this size. Our work extendsmr.mashto require only summary statistics from Genome-Wide Association Studies instead of individual-level data, which are usually publicly available. In addition, the computations using summary statistics do not depend on sample size, making the newly developedmr.mash-rssscalable to extremely large data sets. Using simulations and real data analysis, we show that our method is competitive with other methods for polygenic prediction.
Into the Void: Cavities and Tunnels are Essential for Functional Protein Design
Authors: Zhang Jiahui , Peng Zhengxing
Published: May 2024

The design of functional proteins is crucial as it enables the creation of tailored proteins with specific capabilities, unlocking the potential solutions to various biomedical and industrial challenges. The exact relationship between structure, sequence, and function in protein design is intricate, however, a consensus has been reached that the function of a protein is mostly decided by its structure, which further decides its sequence. While the integration of biology with artificial intelligence has propelled significant advancements in protein design and engineering, structure-based functional protein design, especiallyde novodesign, the quest for satisfactory outcomes remains elusive. In this work, we use backbone geometry to represent the cavities and tunnels of functional proteins and show that they are essential for functional protein design. Correct cavity enables specific biophysical processes or biochemical reactions, while appropriate tunnels facilitate the transport of biomolecules or ions. We also provide a package called CAvity Investigation Navigator (CAIN) to help to do the analysis, which is available athttps://github.com/JiahuiZhangNCSU/CAIN.
Propiconazole and Tianfengsu Regulated the Growth, Flavor, and Nutritionof Brassica rapaby Brassinosteroid Pathway
Authors: Guo Dekang , Gao Qing , Song Yunxue , Liu Zhicheng , Wang Daorui , Xu Hanhong , Lin Fei
Published: May 2024

Propiconazole (PCZ) and Tianfengsu (TFS) are widely used plant growth regulators in vegetable production for improving crop growth, quality, and flavor. This study investigated the effects of PCZ and TFS, applied individually or in combination, on the growth, development, flavor quality, and nutritional components of choy sum (Brassica rapa) andArabidopsis thaliana, as well as the underlying molecular mechanisms. The results showed that PCZ inhibited the growth of choy sum andArabidopsisbut enhanced the accumulation of flavor compounds such as soluble sugars, proteins, and vitamin C. In contrast, TFS promoted plant growth and increased the content of nutritional components, including chlorophyll and unsaturated fatty acids. Notably, the combined application of PCZ and TFS significantly improved overall plant quality, achieving the optimal balance of flavor and nutritional value while maintaining high yield. Transcriptomic analysis revealed the molecular mechanisms of PCZ and TFS in differentially regulating the expression of brassinosteroid (BR) signaling and downstream metabolism-related genes. Weighted gene co-expression network analysis (WGCNA) further identified key gene modules and hub genes controlling flavor metabolism in choy sum. This study elucidates the synergistic mechanisms of PCZ and TFS in regulating vegetable growth and quality formation, providing valuable insights for the safe production of high-quality choy sum and the development of novel plant growth regulators or elite varieties.

HIGHLIGHTS

PCZ and TFS treatments differentially modulate choy sum growth and development by regulating the BR pathway, with PCZ inhibiting while TFS promoting growth.

PCZ enhances the accumulation of soluble sugars, soluble proteins, and vitamin C, while TFS increases photosynthetic pigments and unsaturated fatty acids, synergistically improving the flavor and nutritional quality of choy sum.

Transcriptomic analysis and WGCNA uncover key genes and modules controlling flavor metabolism in choy sum, providing potential targets for developing novel plant growth regulators or breeding elite varieties
Changes in TP53 gene, telomere length, mitochondrial DNA, and its amount in benign prostatic hyperplasia patients
Authors: Zole Egija , Baumanis Edgars , Freimane Lauma , Dāle Rolands , Leiše Andrejs , Lietuvietis Vilnis , Ranka Renāte
Published: May 2024

Benign prostatic hyperplasia (BPH) is a growing issue due to an ageing population; however, there are not enough studies connecting it with ageing hallmarks. Some of the ageing hallmarks are changes in telomere length (TL) and genetic changes like possible mutations in theTP53gene or mitochondrial genome (mtDNA). Our study investigated these factors to see if they could be linked with BPH.

Prostate tissue samples were obtained from 32 patients with BPH (and 30 blood samples). As a healthy control group, age-matching blood DNA samples were used. For mtDNA sequence data comparison, 50 samples of a general Latvian population were used. The full mtDNA genome was sequenced using Next Generation Sequencing (NGS), forTP53gene – Sanger sequencing, and for mtDNA amount and telomere length – qPCR assay.

BPH patients in prostate tissue had much higher TL than in blood cells, and the healthy controls had the shortest telomeres. Also, the mtDNA amount in BPH prostate tissue was the highest compared with blood, and controls had the smallest amount. In theTP53gene, we did not find any mutations that could be linked to BPH. In the mtDNA genome, we found several unique mutations and heteroplasmic changes, as well as changes that have been linked before with prostate cancer (PC).

In conclusion, prolonged telomeres and changes in mtDNA amount might be involved in the development of BPH. Concerning mtDNA genome changes, some of the heteroplasmic or homoplasmic variants might contribute to the development of BPH. More studies should be conducted to prove or disapprove of these connections.
Multiomic Screening Unravels the Immunometabolic Signatures and Drug Targets of Age-Related Macular Degeneration
Authors: Cui Xuehao , Zhao Qiuchen , Mahata Bidesh , Wen Dejia , Yu-Wai-Man Patrick , Li Xiaorong
Published: May 2024

Age-related macular degeneration (AMD) is a significant cause of visual impairment in the aging population, with the pathophysiology driven by a complex interplay of genetics, environmental influences and immunometabolic factors. These immunometabolic mechanisms, in particular, those distinguishing between the dry and wet forms of AMD, remain incompletely understood. Utilizing an integrated multiomic approach, incorporating Mendelian Randomization (MR) and single-cell RNA sequencing (scRNA-seq), we have effectively delineated distinct immunometabolic pathways implicated in the development of AMD. Our comprehensive analysis indicates that the androgen-IL10RA-CD16+ monocyte axis could protect against wet AMD. We have also identified several immune and metabolic signatures unique to each AMD subtype, with TNFα and Notch signaling pathways being central to disease progression. Furthermore, our analysis, leveraging expression Quantitative Trait Loci (eQTLs) from the Genotype-Tissue Expression (GTEx) project coupled with MR, have highlighted genes such asMTOR,PLA2G7,MAPKAPK3,ANGPTL1, andARNTas prospective therapeutic targets. The therapeutic potential of these candidate genes was validated with observations from existing drug trial databases. Our robust genetic and transcriptomic approach has identified promising directions for novel AMD interventions, emphasizing the significance of an integrated multiomic approach in tackling this important cause of visual impairment.