bluuebunny/crossref_metadata_2025 huggingface dataset:
Practice Variability in Uptake and Implementation of New U.S. DHHS Guidelines for Feeding of HIV-Exposed Infants
Authors: Rozen Eisenberg Ilan , Campbell Jeffrey I , Clarke Diana , Cooper Ellen R , Pelton Stephen I , Vuppula Sharon S
Published: December 2024

New U.S. guidelines support shared decision-making regarding breastfeeding for mothers living with HIV and their neonates. We surveyed Pediatric Infectious Diseases Society members about the implementation of these guidelines. We found heterogeneity in uptake, variability in clinical practice, and concerns about implementation. Future research should address these policy-practice gaps.
Quantification of beam size impact on intensity-modulated proton therapy with robust optimization in head and neck cancer—comparison with intensity-modulated radiation therapy
Authors: Baba Hiromi , Hotta Kenji , Takahashi Ryo , Motegi Kana , Sugama Yuya , Sakae Takeji , Tachibana Hidenobu
Published: December 2024

We assessed the effect of beam size on plan robustness for intensity-modulated proton therapy (IMPT) of head and neck cancer (HNC) and compared the plan quality including robustness with that of intensity-modulated radiation therapy (IMRT). IMPT plans were generated for six HNC patients using six beam sizes (air-sigma 3–17 mm at isocenter for a 70–230 MeV) and two optimization methods for planning target volume-based non-robust optimization (NRO) and clinical target volume (CTV)-based robust optimization (RO). Worst-case dosimetric parameters and plan robustness for CTV and organs-at-risk (OARs) were assessed under different scenarios, assuming a ± 1–5 mm setup error and a ± 3% range error. Statistical comparisons of NRO-IMPT, RO-IMPT and IMRT plans were performed. In regard to CTV-D99%, RO-IMPT with smaller beam size was more robust than RO-IMPT with larger beam sizes, whereas NRO-IMPT showed the opposite (P < 0.05). There was no significant difference in the robustness of the CTV-D99% and CTV-D95% between RO-IMPT and IMRT. The worst-case CTV coverage of IMRT (±5 mm/3%) for all patients was 96.0% ± 1.4% (D99%) and 97.9% ± 0.3% (D95%). For four out of six patients, the worst-case CTV-D95% for RO-IMPT (±1–5 mm/3%) were higher than those for IMRT. Compared with IMRT, RO-IMPT with smaller beam sizes achieved lower worst-case doses to OARs. In HNC treatment, utilizing smaller beam sizes in RO-IMPT improves plan robustness compared to larger beam sizes, achieving comparable target robustness and lower worst-case OARs doses compared to IMRT.
Comparison of single- and multi-isocenter planning with Dynamic WaveArc for multiple brain metastases
Authors: Terabe Mitsuaki , Kamomae Takeshi , Taniguchi Yuki , Ichikawa Hajime , Yamada Takehiro , Miyachi Takayuki , Miyauchi Risei , Ito Junji , Ishihara Shunichi
Published: December 2024

Dynamic WaveArc (DWA) is a technique used for continuous, non-coplanar volumetric-modulated arc therapy on the Vero4DRT platform. This study aimed to evaluate the application of single-isocenter DWA (SI-DWA) for treating multiple brain metastases by comparing dose distribution and irradiation time with multi-isocenter DWA (MI-DWA) through retrospective treatment planning. Treatment plans were developed for SI-DWA and MI-DWA in 14 cases with 3–5 brain metastases. Parameters assessed included target dose indices, such as conformity index (CI) of the planning target volume (PTV), volumes of normal brain excluding gross tumor volumes (GTVs) receiving a single dose equivalent of 14 Gy (V14), V30%, V20%, V10%, volumes of normal brain, including GTVs receiving a single dose equivalent of 12 Gy (V12), D2% for other organs at risk, and beam-on time. SI-DWA showed inferior CI, V14, and V12 values for lesions with PTV volumes <1 cc, whereas it performed equivalently to MI-DWA for lesions with PTV volumes ≥1 cc. SI-DWA resulted in higher volumes of normal brain receiving low doses compared to MI-DWA. SI-DWA exhibited significantly shorter beam-on times than MI-DWA. In conclusion, SI-DWA is an effective method for treating multiple brain metastases with PTV volumes ≥1 cc, offering an index of radiation-induced brain necrosis comparable with MI-DWA while allowing for shorter irradiation times.
Endoscopic management to different isolated sphenoid fungal pathologies: case series of a tertiary hospital
Authors: Alabdulaal Maria , AlMuhanna Zahra , AlNaimi Shaykhah , Alkhatib Abdulrhaman , Almomen Ali
Published: December 2024

Isolated sphenoid sinus disease (ISSD) is a rare condition that accounts for roughly 3% of all sinusitis cases. ISSD is predominantly caused by infectious and inflammation processes, with underlying fungal pathologies. This case series aims to illustrate the endonasal endoscopic management of different isolated sphenoid fungal pathologies. We described four distinct case presentations of ISSD at a tertiary hospital in Dammam, Saudi Arabia. These cases included isolated sphenoid fungal ball, allergic fungal sinusitis, and acute invasive fungal sinusitis. The management of isolated sphenoid fungal pathologies differs depending on the type of the disease necessitating early identification and adequate treatment. The endonasal endoscopic approach is successful with minimal complications and favorable outcomes.
A multicenter evaluation of penile curvature correction in men with Peyronie’s disease undergoing inflatable penile prosthesis placement
Authors: Hammad Muhammed A M , Barham David W , Simhan Jay , Nguyen Tuan , Swerdloff Daniel , Miller Jake , Hatzichristodoulou Georgios , Sempels Maxime , Andrianne Robert , Hotaling James M , Hsieh Tung-Chin , Jones James M , Modgil Vaibhav , Osmonov Daniar , Pearce Ian , Perito Paul , Sadeghi-Nejad Hossein , Suarez-Sarmiento Jr Alfredo , Yafi Faysal A , Gross Martin S
Published: December 2024

Background

Inflatable penile prosthesis (IPP) insertion is recommended for the treatment of patients with Peyronie’s disease (PD) and significant erectile dysfunction (ED); adjunctive procedures can be used for residual curvature after IPP placement.

Aim

To assess the management of penile curvature correction in PD patients undergoing IPP procedures within a large multinational, multicenter cohort.

Methods

A retrospective analysis was conducted on PD patients treated with IPP by 11 experienced prosthetic surgeons. Demographic, intraoperative, and postoperative data were analyzed to assess the improvement in penile curvature following IPP, including adjunctive correction techniques such as manual modeling, tunica albuginea plication, and grafting.

Outcomes

Curvature correction achieved after IPP placement and adjunctive procedures.

Results

For 499 PD patients treated with IPP, median age was 62.0 [30.0, 91.0] years with mean follow-up of 16.5 (SD = 12.9) months. The mean preoperative curvature was 39.4° (SD = 17.8°), with dorsal curvature being most common. Among our cohort, 17.6% had IPP-only placement, while the majority of 82.4% patients underwent IPP along with adjunctive correction procedures. Specifically, manual modeling (with/without the “scratch” technique) was used in 74.7% of cases, tunica albuginea plication in 4.8%, grafting in 2%, and combined grafting and modeling in 0.8%. Patients who underwent grafting generally had fewer preoperative comorbidities and more severe preoperative curvatures of 60.0° [45.0°, 70.0°]. Grafting also provided the highest median curvature correction of 55.0° [48.8°, 73.8°], (P < .001). Plication achieved a median curvature correction of 40.0° [28.8°, 41.2°], whereas modeling resulted in a median curvature reduction of 26.0° [20.0°, 39.5°], (P < .001).

Clinical Implications

We observed that grafting, though less frequently used, provided more curvature correction in severe PD cases undergoing IPP.

Strengths and Limitations

Large cohort size and multinational participation are strengths, though retrospective design and general variability in surgical techniques are limitations.

Conclusion

Adjunctive techniques, including grafting, plication, and modeling provide options for tailoring curvature correction to disease severity and patient characteristics. Future prospective studies are needed to standardize and evaluate the comparative outcomes of these techniques.
Comparative renoprotective effectiveness of allopurinol and febuxostat among hyperuricaemic patients with preserved kidney function
Authors: Takayama Atsushi , Fukasawa Toshiki , Takeuchi Masato , Kawakami Koji
Published: December 2024

Objectives

Early initiation of xanthine oxidase inhibitors may benefit patients with preserved kidney function. However, a direct comparison between the impact of allopurinol and that of febuxostat on long-term kidney function among this population is lacking.

Methods

We conducted a retrospective cohort study with a new-user, active-comparator design among patients with estimated glomerular filtration rate (eGFR) within the reference range and no proteinuria. The primary outcome was a composite incidence of significant eGFR decline (≥40% decline from baseline) and all-cause death at 5 years. Adjusted hazard ratios were estimated using Cox’s proportional hazard models with inverse probability of treatment and censoring weighting.

Results

We analysed 1142 patients (287 with allopurinol and 855 with febuxostat). The adjusted hazard ratios (95% confidence intervals) for allopurinol initiators compared to febuxostat initiators for the composite outcome at 5 years were 0.84 (0.74–0.95). The cause-specific adjusted hazard ratios for allopurinol initiators relative to febuxostat initiators were 0.82 (0.70–0.94) for significant eGFR decline >5 years and 1.08 (0.91–1.24) for all-cause death >5 years.

Conclusions

Allopurinol initiators preserved kidney function better than febuxostat >5 years. Clinicians should exercise caution not only when prescribing but also when selecting xanthine oxidase inhibitors, even for patients with preserved kidney function.
Diversity and evolution of viroids and viroid-like agents with circular RNA genomes revealed by metatranscriptome mining
Authors: Koonin Eugene V , Lee Benjamin D
Published: December 2024

Viroids, the agents of several plant diseases, are the smallest and simplest known replicators that consist of covalently closed circular (ccc) RNA molecules between 200 and 400 nucleotides in size. Viroids encode no proteins and rely on host RNA polymerases for replication, but some contain ribozymes involved in replication intermediate processing. Although other viroid-like agents with cccRNAs genomes, such as satellite RNAs, ribozyviruses and retrozymes, have been discovered, until recently, the spread of these agents in the biosphere appeared narrow, and their actual diversity and evolution remained poorly understood. Extensive, targeted metatranscriptome mining dramatically expanded the known diversity of cccRNAs genomes. These searches identified numerous, diverse viroid-like cccRNAs, many found in environments devoid of plant and animal material, suggesting replication in unicellular eukaryotic and/or prokaryotic hosts. Several cccRNAs are targeted by CRISPR systems, supporting their association with bacteria. In addition to small cccRNAs in the viroid size range, a broad variety of ribozyviruses and novel viruses with cccRNAs genomes, with genomes reaching nearly 5 kilobases, were discovered. Thus, metatranscriptome mining shows that the diversity of viroid-like cccRNAs genomes is far greater than previously suspected, prompting reassessment of the relevance of these replicators for understanding the primordial RNA world.
Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV
Authors: Silva-Klug Ana C , Paytubi Sònia , Torres Montserrat , Trenti Loris , Baixeras Nuria , Sanchez-Llamas Monica , Pavon Miquel A , De Sanjose Silvia , Catala Isabel , Vidal August , Poljak Mario , Alemany Laia , Podzamczer Daniel , Videla Sebastian , Saumoy Maria
Published: December 2024

Background

This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods

This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing. Three screening procedures were compared with aLBC: biomarker alone, cytology and biomarker in all, and cytology and reflex biomarkers (biomarkers applied if aLBC results were atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion). Biomarkers included Linear Array (LA), LA for 14 high-risk human papillomavirus (LA 14 HR-HPV) genotypes, LA HPV-16, Hybrid Capture 2 (HC2), E6/E7 mRNA, and E6/E7 mRNA HPV-16.

Results

Of 354 participants, 179 (50.6%) had atypical squamous cells of undetermined significance or worse, requiring HRA (sensitivity, 80%; specificity, 57.3%; area under the curve, 0.687; reference, biopsy-proven HSIL). Cytology and reflex biomarkers per E6/E7 mRNA, LA 14 HR-HPV, and HC2 and the biomarker-alone procedure with HC2 showed comparable accuracy (sensitivities: 71.6%, 78.8%, 73.1%, 75.7%; specificities: 73.5%, 67.9%, 76.1%, 65.5%; areas under the curve: 0.726, 0.734, 0.746, 0.706) with fewer HRA referrals (number needed to diagnose: 2.2, 2.1, 2, 2.4).

Conclusions

Our findings suggest that E6/E7 mRNA, LA 14 HR-HPV, and HC2 in the cytology and reflex biomarkers procedure, as well as HC2 in the biomarker-alone procedure, can improve anal HSIL screening effectiveness.
Prospective Trial of a Passive Diversion Device to Reduce Blood Culture Contamination
Authors: Arnaout Sami , Stock Shannon , Clifford Julia M , Greenough Thomas C , Wedig Azalea , Mitchell Michael J , Ellison Richard T
Published: December 2024

Background

Blood culture contaminants can lead to inappropriate antibiotic use, prolonged length of stay, and additional hospital costs. Several devices have been developed to reduce the risk of blood culture contamination by diverting a portion of the initial blood sample from the blood culture bottle. We assessed the effectiveness of 1 blood diversion device (BDD) in a prospective trial performed at the 2 separate emergency departments (EDs) of an academic medical center.

Methods

A multiphase prospective crossover trial was performed with the BDD in use at 1 ED and standard equipment at the other ED for 10 weeks, and a second 10-week study phase was conducted with the use of the BDD and standard equipment in the EDs reversed. Contaminants were identified both by standard clinical microbiology lab criteria and by independent retrospective review by 3 infectious disease (ID) physicians. The primary analysis was performed based on intention-to-use data using the physician review of positive blood cultures.

Results

A total of 5637 blood samples were obtained, with 5625 samples analyzed after 12 blood culture results were deemed inconclusive by the ID physician review. The University ED had a higher blood culture contamination rate of 2.9% compared with the Memorial ED at 1.4%. In an intention-to-use analysis, the overall contamination rates were 2.0% and 2.9% in the BDD and standard equipment periods, respectively (P = .03), and in an actual-use analysis the contamination rates were 1.2% and 3.0% for the BDD and standard equipment, respectively (P < .001).

Conclusions

The BDD was associated with significantly lower blood culture contamination rates at the institution's 2 EDs, with a stronger effect noted at the campus caring for higher acuity patients.
Identifying High-Risk Populations for Sexually Transmitted Infections in Chinese Men Who Have Sex With Men: A Cluster Analysis
Authors: Lu Fang , She Bingyang , Zhao Rui , Li Gaixia , Hu Yawu , Liu Yi , Zhao Min , Zhang Lei
Published: December 2024

Background

This study aimed to identify subpopulations of Chinese men who have sex with men (MSM) with distinct sexual behavioral patterns and explore their correlations with sexually transmitted infections (STIs).

Methods

We recruited 892 eligible MSM in Xi'an, China, collecting sociodemographic, sexual behavior, and STI data. Cluster analysis identified distinct sexual behavioral patterns, allowing us to examine STI differences across clusters.

Results

Among the 892 MSM analyzed, 3 clusters were identified. Cluster 1 (n = 157) exhibited high-risk sexual behavioral patterns, including the highest median number of sexual partners (5 vs 1 in cluster 2 vs 3 in cluster 3, P < .001), lowest consistent condom use for insertive anal sex (0% vs 64.12% vs 99.76%, P = .004) and receptive anal sex (9.22% vs 67.71% vs 98.91%, P = .006), highest uncertainty of partners' STIs (77.07% vs 57.89% vs 64.5%, P < .001), all recent partners being casual, longest length of sequential sexual acts (6 vs 5 vs 5, P = .045), and highest rates of gonorrhea (20.38% vs 10.09% vs 14.99%, P = .019) and chlamydia (16.56% vs 8.33% vs 13.21%, P = .045). Cluster 2 (n = 228) showed the lowest engagement in high-risk behaviors and STIs, characterized by the fewest sexual partners, highest certainty of partner's STIs, and all recent partners being regular. Cluster 3 (n = 507) showed moderate levels of high-risk behaviors and STIs, with the highest consistent condom use during anal sex.

Conclusions

This study identified 3 subpopulations of Chinese MSM with distinct sexual behavioral patterns. Targeted public health interventions to the most at-risk subpopulations of MSM are essential for STI prevention.
Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study
Authors: Zugman Miguel , McDermott David F , Escudier Bernard J , Hutson Thomas E , Porta Camillo , Verzoni Elena , Atkins Michael B , Rini Brian , Pal Sumanta K
Published: December 2024

Background

The phase III TIVO-3 study demonstrated improvement in progression-free survival (PFS) with tivozanib compared with sorafenib in patients with 2-3 prior systemic regimens for metastatic renal cell carcinoma (mRCC).

Methods

The TIVO-3 trial enrolled patients with measurable mRCC who had received 2 or more prior systemic therapies, including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Patients were stratified by International Metastatic RCC Database Consortium risk score and type of prior treatment and were randomized 1:1 to receive tivozanib or sorafenib. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 criteria, with PFS as the primary endpoint. Safety was evaluated using Common Terminology Criteria for Adverse Events version v4.03, and statistical analyses included Cox regression for overall survival (OS) and descriptive statistics for duration of response (DOR). The current post-hoc long-term follow-up analysis consists of an assessment of OS in the previously stratified subpopulation of patients with prior CPI exposure.

Results

Between May 2016, and August 2017, 350 patients were randomized, of which 26% had prior CPI exposure, with final analysis data cut off on June 21, 2021. In patients previously treated with CPIs (n = 91), the median PFS of tivozanib was 7.3 months versus 5.1 months with sorafenib and hazard ratio (HR) of 0.55 (95% CI, 0.32-0.94). The OS HR in the CPI-treated subset was 0.69 (95% CI, 0.43-1.11, P =.0992) favoring tivozanib, although with a median OS of 18.1 and 20.9 months, for tivozanib and sorafenib, respectively. Tivozanib demonstrated a longer median DOR of 20.3 versus 5.7 months for sorafenib in the subset previously treated with CPIs. The safety profile favored tivozanib, with lower rates of VEGF-TKI class-related grade ≥3 adverse events compared with sorafenib. However, in the subset of patients previously treated with CPIs, the incidence of grade ≥3 adverse events was higher, at 58% for tivozanib and 67% for sorafenib, compared with the ITT population, at 46% and 55%, respectively.

Conclusions

In this long-term post-hoc update of the TIVO-3 trial, we show that in CPI-resistant mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with improved OS data, although not statistically significant, and durable responses.
InsectNet: Real-time identification of insects using an end-to-end machine learning pipeline
Authors: Chiranjeevi Shivani , Saadati Mojdeh , Deng Zi K , Koushik Jayanth , Jubery Talukder Z , Mueller Daren S , O’Neal Matthew , Merchant Nirav , Singh Aarti , Singh Asheesh K , Sarkar Soumik , Singh Arti , Ganapathysubramanian Baskar
Published: December 2024

Insect pests significantly impact global agricultural productivity and crop quality. Effective integrated pest management strategies require the identification of insects, including beneficial and harmful insects. Automated identification of insects under real-world conditions presents several challenges, including the need to handle intraspecies dissimilarity and interspecies similarity, life-cycle stages, camouflage, diverse imaging conditions, and variability in insect orientation. An end-to-end approach for training deep-learning models, InsectNet, is proposed to address these challenges. Our approach has the following key features: (i) uses a large dataset of insect images collected through citizen science along with label-free self-supervised learning to train a global model, (ii) fine-tuning this global model using smaller, expert-verified regional datasets to create a local insect identification model, (iii) which provides high prediction accuracy even for species with small sample sizes, (iv) is designed to enhance model trustworthiness, and (v) democratizes access through streamlined machine learning operations. This global-to-local model strategy offers a more scalable and economically viable solution for implementing advanced insect identification systems across diverse agricultural ecosystems. We report accurate identification (>96% accuracy) of numerous agriculturally and ecologically relevant insect species, including pollinators, parasitoids, predators, and harmful insects. InsectNet provides fine-grained insect species identification, works effectively in challenging backgrounds, and avoids making predictions when uncertain, increasing its utility and trustworthiness. The model and associated workflows are available through a web-based portal accessible through a computer or mobile device. We envision InsectNet to complement existing approaches, and be part of a growing suite of AI technologies for addressing agricultural challenges.
The Role of Fatty Acid Amide Hydrolase, a Key Regulatory Endocannabinoid Enzyme, in Domain-Specific Cognitive Performance in Psychosis
Authors: Weidenauer Ana , Garani Ranjini , Lalang Nittha , Watts Jeremy , Lepage Martin , Rusjan Pablo M , Mizrahi Romina
Published: December 2024

Background and Hypothesis

Cognitive impairments are particularly disabling for patients with a psychotic disorder and often persist despite optimization of antipsychotic treatment. Thus, motivating an extension of the research focus on the endocannabinoid system. The aim of this study was to evaluate group differences in brain fatty acid amid hydrolase (FAAH), an endocannabinoid enzyme between first-episode psychosis (FEP), individuals with clinical high risk (CHR) for psychosis and healthy controls (HCs). Furthermore, to test the hypothesis that FAAH is linked with cognition using positron emission tomography (PET).

Study Design

We analyzed 80 PET scans with the highly selective FAAH radioligand [11C]CURB, including 30 patients with FEP (6 female), 15 CHR (5 female), and 35 HC (19 female). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Berg Card Sorting Test (BCST) were applied to test cognitive performance.

Study Results

There was no difference in FAAH activity between groups (F2, 75 = 0.75, P = .48; Cohen’s f = 0.141; small effect). Overall, there was a difference in the association between groups regarding FAAH activity and the domain visuospatial construction (F2, 72 = 4.67, P = .01; Cohen’s f = .36; medium effect). Furthermore, across the sample, lower FAAH activity was associated with a higher percentage of perseverative responses (F1, 66 = 5.06, P = .03; Cohen’s f = 0.28, medium effect).

Conclusions

We report evidence for associations between endocannabinoid alterations in FEP and CHR with specific domains of cognition (visuospatial construction and perseverative response), not overall cognition.
The National Early Warning Score 2 versus the New-Poisoning Mortality Score System for Predicting Clinical Outcomes After Acute Aluminum Phosphide Poisoning
Authors: Nafea Ola Elsayed , Ibrahim Fatma , Abdelhamid Walaa G
Published: December 2024

Acute aluminum phosphide (AlP) poisoning is one of the leading causes of suicide, particularly in the developing world. In cases of scarce and/or high-cost resources, it is advisable to prioritize critically ill patients who will benefit from available resources and improve their prognosis. Despite numerous scores, a dependable, easy-to-use, and quick approach to assessing the degree of poisoning is lacking. This study is designed to compare the prognostic performance of the National Early Warning Score 2 (NEWS2) versus the new-poisoning mortality score system (new-PMS) for predicting the clinical outcomes, including in-hospital mortality, vasopressor use, and mechanical ventilation placement after acute AlP poisoning. This study was a retrospective observational study that included patients with acute AlP poisoning with retrieving the required data from the patients' medical records. A total of 90 acutely AlP-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 42.2%. Additionally, in-hospital mortality, vasopressor use, and mechanical ventilation placement were significantly higher in patients with higher NEWS2 and new-PMS scores. The new-PMS showed excellent prognostic performance, particularly in-hospital mortality prediction; however, NEWS2 demonstrated a more helpful predictive performance compared to the new-PMS particularly for the need for mechanical ventilation and in-hospital mortality, with an area under the curve of 0.991 versus 0.851 and 0.949 versus 0.874, respectively. We concluded that NEWS2 and new-PMS are simple, easily calculated, and lab-independent scoring systems. The NEWS2 is a more effective tracking and triggering tool than the new-PMS in the evaluation of AlP acutely intoxicated patients.
CRISPR/Cas system and its application in the diagnosis of animal infectious diseases
Authors: Rasool Hafiz Muhammad Hamza , Chen Qiwei , Gong Xiaowei , Zhou Jizhang
Published: December 2024

Infectious diseases are a serious threat to the existence of animals and humans' life. In the 21st century, the emergence and re‐emergence of several zoonotic and non‐zoonotic global pandemic diseases of socio‐economic importance has affected billions of humans and animals. The need for expensive equipment and laboratories, non‐availability of on‐site testing abilities, with time‐consuming and low sensitivity and specificity issues of currently available diagnostic techniques to identify these pathogenic micro‐organisms on a large scale highlighted the need for developing cheap, portable environment friendly diagnostic methods. In recent years, these issues have been addressed by clustered regularly interspaced palindromic repeats (CRISPR)‐based diagnostic platforms that have transformed the molecular diagnostic field due to their outstanding ultra‐sensitive nucleic acid detecting capabilities. In this study, we highlight the types, potential of different Cas proteins, and amplification systems. We also illuminate the application of currently available CRISPR integrated setups on the diagnosis of infectious diseases, majorly in food‐producing animals (pigs, ruminants, poultry, and aquaculture), domestic pets (dogs and cats), and diseases of zoonotic importance. We conclude the challenges and future perspectives of using these systems to rapidly diagnose and treat other infectious diseases and also develop control strategies to prevent the spread of pathogenic organisms.
Pyridoxine Prevents Postoperative Nausea and Vomiting in Gynecological Laparoscopic Surgery: A Double-blind Randomized Controlled Trial
Authors: Zhang Qirui , Ye Xuyang , Shi Shuqing , Zhou Songhua , Ma Daqing , Ouyang Wen , Tong Jianbin , Le Yuan
Published: December 2024

Background:

Postoperative nausea and vomiting (PONV) are common complications after gynecological laparoscopic surgery. Pyridoxine has been recommended as a first-line drug to prevent and treat nausea and vomiting during pregnancy; however, its efficacy in preventing PONV remains unclear.

Methods:

Patients of 18 to 65 years old, who received elective gynecological laparoscopic surgery under general anesthesia, were randomized into either the pyridoxine or control group. The pyridoxine group received 0.2g vitamin B6 before anesthesia induction, and the control group received normal saline intravenously. Both groups received a similar regimen of combined intravenous and inhalation general anesthesia. All patients received dexamethasone(intravenous) after anesthesia induction and ondansetron(intravenous) before surgery completion. PONV occurrence was recorded according to the patients’ self-reported data. Other clinical data were collected from hospital system, and concentrations of blood interleukin-6 and substance P were measured by ELISA.

Results:

A total of 442 patients were screened and 240 patients were equally randomized to the pyridoxine or control group. The incidence of PONV was statistically significant lower in the pyridoxine group than in the control group (16.7% [20/120] vs. 35.8% [43/120]; relative risk (RR) = 0.47 [95% CI: 0.29, 0.74]; absolute risk reduction (ARR) = 0.20 [95% CI: 0.08, 0.30]; P = 0.001), and pyridoxine decreased the incidence of postoperative nausea (12.5% [15/120] vs. 35% [42/120]; RR = 0.36 [95% CI: 0.21, 0.61]; ARR = 0.23 [95% CI: 0.12, 0.33]; P < 0.001). There were no statistical differences in postoperative vomiting, time to the first PONV occurrence, pain, serum interleukin-6 and substance P, and white blood cell and neutrophil counts.

Conclusion:

In this single center randomized trial, pyridoxine plus dexamethasone and ondansetron reduced the incidence of PONV in patients undergoing elective gynecological laparoscopic surgery under general anesthesia. These findings need to be validated in multicenter studies in diverse populations to ensure generalizability.
Endocannabinoids and atherosclerosis: the future of therapeutic strategies—a review
Authors: Umesh Sri Vaishnavi
Published: December 2024

The endocannabinoid system (ECS) is a widespread cell signaling system in the human body, composed of the endocannabinoid molecules-anandamide, 2-arachidonoyl glycerol, their primary receptors, and the associated enzymes responsible for synthesis and degradation. Together, these components of the ECS work harmoniously to maintain homeostasis. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with atherosclerosis as the principal risk factor. Atherosclerosis is a progressive disease characterized by the formation of lipid-rich plaques within the walls of medium and large vessel arteries. This process begins with endothelial damage and, progresses through a cascade of events, including lipid accumulation, fibrosis, and calcification, that leads to vessel narrowing and inflammation. The resulting atheromatous plaque, along with complications such as rupture, thrombosis, or embolism contributes to serious cardiovascular outcomes. The role of endocannabinoids in cardiovascular pathology, particularly through the cannabinoid (CB) 1 and 2 receptors has gained attention. Studies have shown that CB1 receptors are pro-atherogenic while CB2 receptors exhibit anti-atherogenic properties. Activation of the ECS, especially under ischemic conditions, promotes CB1 expression and free radical production, which damages endothelial cells and accelerates the development of atherosclerosis. Inhibition of specific ECS receptors and enzymes has shown promise in reducing atherosclerosis complications, as evidenced by outcomes from major clinical trials (the Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant - the Intravascular Ultrasound Study [STRADIVARIUS]). These findings suggest that targeting the ECS may offer a novel therapeutic approach to managing atherosclerosis.
Physical Therapy Outcome Measures Used in Persons With Long Covid: A Systematic Review of Interventional Studies Up to 1-Year Postglobal Health Emergency
Authors: Lopes Sauers Andrea , Johnson Liana , Mortensen Marissa , da Silva Laura Bianca Dorásio , de Jesus Luciana Angélica da Silva , González Jaime , Oliveira Cristino
Published: December 2024

Purpose:

To identify the most frequently used outcome measures in interventional studies for Long Covid in outpatient, home-based, and telerehabilitation physical therapy settings.

Methods:

Registered in PROSPERO (registration number: CRD42021286714) and conducted according to PRISMA guidelines, this review included interventional studies performed in outpatient, telerehabilitation, or home-based physical therapy settings, assessing adults with persistent Long Covid symptoms in at least 3 months post-COVID-19 infection and published in English, Spanish, or Portuguese. A comprehensive search strategy was executed across PubMed, Embase, Scopus, PEDro, SciELO, Web of Science, and CINAHL. Data were managed via Covidence, with studies independently screened and extracted by multiple authors. The risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool. Outcome measures were mapped to constructs based on core outcome sets (COS) for Long Covid by an international Delphi consensus and American Physical Therapy Association Cross Sections and Academies for COVID-19. The frequency of use of each outcome measure, between-group comparisons, clinical meaningfulness, and reference values from previous studies were reported.

Results:

Fourteen studies met the inclusion criteria, utilizing 43 distinct outcome measures to assess constructs such as health-related quality of life, functional mobility, endurance, cognition, mental health, strength/power, and fatigue. Notably, 76.4% (33/43) of these measures were used in only one study, with the EQ-5D being the most frequently employed (50%, 7/14).

Conclusions:

While the outcome measures largely aligned with recommended core domains for Long Covid, significant heterogeneity was observed. Given the variability in outcome measures, the EQ-5D is recommended for assessing health-related quality of life in individuals with Long Covid.
Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy
Authors: Kara Firat , Tosakulwong Nirubol , Lesnick Timothy G. , Fought Angela J. , Kendell-Thomas June , Kapoor Ekta , Faubion Laura L. , Schwarz Christopher G. , Senjem Matthew L. , Fields Julie A. , Min Paul H. , Lowe Val J. , Jack Clifford R. , Bailey Kent R. , James Taryn T. , Lobo Rogerio A. , Manson JoAnn E. , Pal Lubna , Hammers Dustin B. , Malek-Ahmadi Michael , Cedars Marcelle I. , Naftolin Frederick N. , Santoro Nanette , Miller Virginia M. , Harman Sherman M. , Dowling N. Maritza , Gleason Carey E. , Kantarci Kejal
Published: December 2024

Objective

To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods

Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT. The associations between KEEPS baseline blood pressure (BP) with KEEPS continuation WMH volume were examined adjusting for covariates in model 1 (age, total intracranial volume, study site, mHT type) and model 2 (additionally conventional CVD risk factors). Interaction terms (BP × mHT type) were added into the linear regression models.

Results

The mean ± SD ages of participants were 53 (±2) years at KEEPS baseline and 67 (±2) years at KEEPS continuation. Elevated BP at KEEPS baseline was associated with greater WMH volume measured 14 years later (model 1: SBP: β = 0.01 [95% CI, 0.001‐0.01] and DBP: β = 0.01 [95% CI, 0.003‐0.03]) and after additionally adjusting for CVD risk factors (model 2). We did not find any evidence that mHT versus placebo modified these associations. Topographically, higher BP was associated with greater periventricular WMH in the frontal and parietal lobes.

Conclusion

Our findings suggest the importance of maintaining normal BP in recently postmenopausal women with low CVD risk, irrespective of short-term mHT usage, to potentially reduce the risk of WMH later in life.
Co-regulation of Epidermal Permeability Barrier Function and Immune Function: A Narrative Review
Authors: Man Mao-Qiang , Gao Jie-Fang , Zhang Guo-Qiang
Published: December 2024

The epidermal permeability barrier, primarily located in the stratum corneum, is largely determined by keratinocyte function in the epidermis. Various internal and external factors can directly or indirectly influence keratinocyte function, leading to changes in epidermal permeability barrier function. Among internal factors, cytokines and immune cells can both positively and negatively regulate this barrier. Conversely, epidermal permeability barrier function also influences cytokine expression and immune cell activity. Studies show that increased IL-1α expression or topical application of IL-6 and TNF-α accelerates epidermal permeability barrier repair in acutely disrupted skin. Additionally, mast cells and Toll-like receptor 2 are essential for formation of the epidermal permeability barrier. However, IL-4, IL-22, and histamine impair its function. Disruption of the epidermal permeability barrier further amplifies cytokine expression, T-cell maturation, and inflammatory cell infiltration in the skin. Thus, epidermal permeability barrier function and immune function co-regulate each other, with proper management of one benefiting the other. This review briefly summarizes the evidence for this co-regulation and its clinical significance.
Understanding the mechanism of disease of vitiligo and the impact on clinical management
Authors: McElroy Jameka , Casquejo Robert J. , Yu Henry , Torsiello Janel , Sangha Archana M. , Bush Laura P.
Published: December 2024

Vitiligo is a depigmenting skin condition that affects 0.5% to 2.0% of the global population and can significantly affect quality of life. Although vitiligo may be dismissed as cosmetic or untreatable, pathogenesis is driven by immunologic mechanisms that can be blocked with treatment, leading to skin repigmentation. The disease typically begins with genetic or environmental factors that induce skin cell stress, which initiates a cascade of immune events resulting in the recruitment of T cells to the skin and the destruction of melanocytes. Various treatment options exist that can block this autoimmune attack and allow repigmentation to occur over time. However, given the complexity of vitiligo pathogenesis, many patients do not fully understand their disease, how repigmentation can be achieved, or why repigmentation is a slow process that requires long-term treatment. Furthermore, dermatology health care providers may find it difficult to explain the underlying disease mechanism of vitiligo or answer patient questions about treatment. Better education about vitiligo and repigmentation mechanisms is crucial for successful disease management. This review aims to summarize what is known about vitiligo pathogenesis and current treatment options so dermatology health care providers can help patients manage their vitiligo with realistic expectations. Supplemental materials include additional information that can be shared with patients.
Patient-reported outcome based symptom management is a better option for early postoperative recovery after breast cancer surgery: a parallel controlled randomized clinical trial
Authors: Wang Weiwei , Ma Xingcong , Shan Changyou , Du Chong , Zhou Zhangjian , Yan Wanjun , Zhao Fang , Liang Baobao , He Rui , Chai Yichao , Mao Guochao , Zhao Yonglin , Yang Congying , Yang Ying , Zhang Tianxiao , Zhang Shuqun
Published: December 2024

Background:

We aimed to assess the efficacy and feasibility of applying patient-reported outcome (PRO) based symptom management in the early postoperative period after breast cancer surgery.

Materials and methods:

Before surgery, patients diagnosed with breast cancer who met the inclusion criteria were randomly assigned in a 1:1 ratio to receive either postoperative PRO-based symptom management or usual care. All patients completed the MD Anderson Symptom Inventory-Chinese version (MDASI-C) via the electronic PRO system preoperatively, on a daily basis postoperatively, and twice weekly after discharge, for a duration up to 2 weeks. In the PRO-based care group, in addition to receiving usual care, patients whose symptoms reported by completing MDASI-C with a score of ≥4 will be managed symptomatically by the attending surgeon. Patients in the usual care group received routine care and their MDASI-C scores were unknown to their attending surgeon. The primary outcome was the MDASI-C score of patients at the time of discharge. Analyses were conducted in accordance with the established protocol.

Results:

Of the 134 participants, 67 were randomly assigned to each group. At discharge, the total score of MDASI-C scale was significantly higher in the usual care group comapred to the PRO-based care group (median [interquartile range], 22 [19] vs. 35 [36]; P = 0.002). The score of FACT-B scale (adjusted mean difference, 0.39; 95% confidence interval, 0.11–1.06; P = 0.009) was significantly lower in the usual care group than in the PRO-based care group during the 14 days after surgery. In the PRO-based care group, 87.2% of patients found the PRO-based symptom management approach helpful in their early postoperative recovery.

Conclusion:

The implementation of a PRO-based symptom management system within 2 weeks after breast cancer surgery effectively alleviates symptom burden and improves quality of life compared to usual care.
The association between diabetes mellitus and postoperative cognitive dysfunction: a systematic review and meta-analysis
Authors: Liu Hongbo , Chen Jiali , Ling Jitao , Wu Yuting , Yang Pingping , Liu Xiao , Liu Jianping , Zhang Deju , Yin Xiaoping , Yu Peng , Zhang Jing
Published: December 2024

Background:

Postoperative cognitive dysfunction (POCD) is a typical consequence following surgery, particularly in cardiac surgeries. Despite its high incidence, the underlying aetiology remains unclear. While diabetes mellitus (DM) has been associated with cognitive impairment, its specific function in POCD development remains unidentified. This study aims to evaluate the connection between DM and the risk of POCD.

Methods:

We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library databases for studies of DM and risk with POCD, collecting data up to 14 September 2023. We assessed publication bias, heterogeneity, and study quality, adhering to PRISMA and AMSTAR guidelines.

Results:

Our study comprised 38 trials involving 8748 individuals, with 7734 patients undergoing follow-up. The pooled results showed that individuals with DM had an increased incidence of POCD compared to nondiabetic individuals (RR: 1.44, 95% CI: 1.26–1.65). The incidence of POCD was significantly higher in the group of patients with an average age older than 65 years (RR: 1.69, 95% CI: 1.30–2.20) compared with diabetic patients with an average age younger than 65 years (RR: 1.29, 95% CI: 1.09–1.64). Compared with diabetic patients undergoing cardiac surgery (RR: 1.33, 95% CI: 1.15–1.53), patients receiving non-cardiac surgery showed a greater incidence of POCD (RR: 2.01, 95% CI: 1.43–2.84).

Conclusion:

Current evidence underscores that diabetic patients face a significantly higher risk of POCD compared to their nondiabetic counterparts. Further research is warranted to clarify the precise mechanisms of this relationship and explore potential preventive strategies for diabetic patients.
Identification of hub biomarkers in liver post-metabolic and bariatric surgery using comprehensive machine learning (experimental studies)
Authors: Li Zhehong , Wang Liang , Tian Chenxu , Wang Zheng , Zhao Hao , Qi Yao , Chen Weijian , Wuyun Qiqige , Amin Buhe , Lian Dongbo , Zhu Jinxia , Zhang Nengwei , Zheng Lifei , Xu Guangzhong
Published: December 2024

Background:

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 30%, and the condition can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Metabolic and bariatric surgery (MBS) has been shown to be effective in treating obesity and related disorders, including NAFLD.

Objective:

In this study, comprehensive machine learning was used to identify biomarkers for precise treatment of NAFLD from the perspective of MBS.

Methods:

Differential expression and univariate logistic regression analyses were performed on lipid metabolism-related genes in a training dataset (GSE83452) and two validation datasets (GSE106737 and GSE48452) to identify consensus-predicted genes (CPGs). Subsequently, 13 machine learning algorithms were integrated into 99 combinations; among which the optimal combination was selected based on the total score of the area under the curve, accuracy, F-score, and recall in the two validation datasets. Hub genes were selected based on their importance ranking in the algorithms and the frequency of their occurrence. Finally, a mouse model of MBS was established, and the mRNA expression of the hub genes was validated via quantitative PCR.

Results:

A total of 12 CPGs were identified after intersecting the results of differential expression and logistic regression analyses on a Venn diagram. Four machine learning algorithms with the highest total scores were identified as optimal models. Additionally, PPARA, PLIN2, MED13, INSIG1, CPT1A, and ALOX5AP were identified as hub genes. The mRNA expression patterns of these genes in mice subjected to MBS were consistent with those observed in the three datasets.

Conclusion:

Altogether, the six hub genes identified in this study are important for the treatment of NAFLD via MBS and hold substantial promise in guiding personalized treatment of NAFLD in clinical settings.