bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between metabolically healthy obesity and metastasis in lung cancer patients – a systematic review and meta-analysis
Authors: Malki Ahmed , Shaik Riyaz Ahamed , Sami Waqas 
Published: October 2023

BackgroundMany clinical trials have looked at the relationship between obesity and lung cancer (LC), however, there is scarcity of literature specifically addressing the association between metabolically healthy obesity and metastasis in LC patients. To address this gap in the body of evidence, the study was conducted to observe the association between metabolically healthy obesity and metastasis in LC patients.MethodsWe conducted a pre-registered systematic review by searching six major online databases to identify studies relevant related to our investigation, in adherence with the PRISMA guidelines. A proper data extraction protocol was further established to synthesize the findings from the selected papers through a meta-analysis.ResultsEleven (11) studies met the requisite selection criterion and were included in the study. A random-effect model was used. Obesity was found to have a significant impact on readmission in LC patients. The combined analysis showed a significant effect size of 0.08 (95% CI 0.07 to 0.08), indicating a noticeable impact of obesity. It was also assessed that obese individuals had a 34% reduced risk of LC compared to normal weight individuals. Obesity was associated with a lower risk of surgical complications with a pooled risk ratio of 0.13 (95% CI 0.12 to 0.14). A statistically significant decreased risk of LC (pooled RR = 0.72, 95% CI: 0.68 to 0.77) was also observed in the obese individuals.ConclusionThe analysis reveals that obesity is associated with a noticeable increase in readmissions, although the impact on LC risk itself is negligible. Moreover, obesity appears to have a beneficial effect by reducing the risk of surgical complications. These results highlight the complex relationship between the two aforementioned factors, emphasizing the importance of considering obesity as a significant factor in patient management and healthcare decision-making.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023427612.
Comprehensive molecular expression profiling of SARS-CoV-associated factors in the endometrium across the menstrual cycle and elevated susceptibility in women with recurrent pregnancy loss
Authors: Qi Ruofan , Guan Rui , Cai Shengyun , Xu Mingjuan , Yang Wen-jui , Wang Chi Chiu 
Published: October 2023

Objective: To evaluate the dynamic expression profiling alterations of SARS-CoV-2-associated molecules within the fertile human endometrium throughout the menstrual cycle. Furthermore, to explore the inherent vulnerability of the endometrium to SARS-CoV-2 infection among women experiencing recurrent pregnancy failure, including both recurrent implantation failures (RIF) and recurrent pregnancy losses (RPL).Method: The present study employed multiple datasets to investigate the expression patterns of SARS-CoV-2-associated genes. Firstly, a single-cell RNA-sequencing dataset comprising endometrial samples from 19 healthy women across the menstrual cycle was utilized. Additionally, two microarray datasets encompassing 24 women with RIF, and 24 women with RPL during the peri-implantation phase were included. To complement these analyses, immunohistochemical (IHC) staining was performed on endometrial samples collected from 30 women with RIF, 30 women with RPL, and 20 fertile controls recruited specifically during the implantation period.Results: The investigation revealed a moderate expression percentage of CTSL (22%), TMPRSS4 (15%), FURIN (16%) and MX1 (9%) in endometrium. Conversely, the expression percentages of ACE2 (1%) and TMPRSS2 (4%) were relatively low. Notably, the expression of BSG exhibited an increment towards the window of implantation, reaching its peak during the middle secretary phase. Furthermore, a significant reduction (p &lt; 0.05) in TMPRSS2 expression was observed in the RIF group compared to the control group. While the expression of BSG was significantly increased (p &lt; 0.05) in the RPL group, findings that were corroborated by the IHC staining results.Conclusion: The findings of this study indicate a noteworthy upregulation of BSG expression in the endometrium of women with RPL. These results suggest an augmented susceptibility of endometrium to SARS-CoV-2 infection, potentially contributing to unfavorable pregnancy outcomes.
Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level
Authors: Cassiano Larissa Marcely Gomes , Oliveira Marina da Silva , de Queiroz Karina Barbosa , Amancio Alice Muglia Thomaz da Silva , Salim Anna Christina de Matos , Fernandes Gabriel da Rocha , Carneiro Cláudia Martins , Coimbra Roney Santos 
Published: October 2023

BackgroundThe interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl.Material and methodsEleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis.ResultsIn this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug.ConclusionB12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.
Training future clinicians in telehealth competencies: outcomes of a telehealth curriculum and teleOSCEs at an academic medical center
Authors: Bajra Rika , Srinivasan Malathi , Torres Elise Cheng , Rydel Tracy , Schillinger Erika 
Published: October 2023

BackgroundThis study describes the program and learning outcomes of a telehealth skills curriculum based on the Association of American Medical Colleges (AAMC) telehealth competencies for clerkship-level medical students.MethodsA total of 133 third- and fourth-year medical students in a required family medicine clerkship at Stanford University School of Medicine participated in a telehealth curriculum, including a telehealth workshop, site-specific telehealth clinical encounters, and telemedicine objective structured clinical examinations (teleOSCEs) between July 2020 and August 2021. Their workshop communication and physical examination competencies were assessed in two teleOSCEs utilizing a novel telehealth assessment tool. Students' attitudes, skills, and self-efficacy were assessed through voluntary pre-clerkship, post-workshop, and post-OSCE surveys.DiscussionMost learners reported low confidence in their telehealth physical examinations [n = 79, mean = 1.6 (scale 0–5, 5 = very confident, SD = 1.0)], which improved post-workshop [n = 69, 3.3 (0.9), p &lt; 0.001]; almost all (97%, 70/72) felt the workshop prepared them to see patients in the clinic. In formative OSCEs, learners demonstrated appropriate “webside manner” (communication scores 94–99%, four items) but did not confirm confidentiality (21%) or review limitations of the visit (35%). In a low back pain OSCE, most learners assessed pain location (90%) and range of motion (87%); nearly half (48%) omitted strength testing.ConclusionOur telehealth curriculum demonstrated that telehealth competencies can be taught and assessed in medical student education. Improvement in self-efficacy scores suggests that an 80-min workshop can prepare students to see patients in the clinical setting. Assessment of OSCE data informs opportunities for growth for further development in the curriculum, including addressing visit limitations and confidentiality in telehealth visits.
Survival outcomes and mobilization during venovenous extracorporeal membrane oxygenation: a retrospective cohort study
Authors: Rottmann Felix A. , Noe Christian , Bemtgen Xavier , Maier Sven , Supady Alexander , Wengenmayer Tobias , Staudacher Dawid L. 
Published: October 2023

IntroductionVenovenous extracorporeal membrane oxygenation (V-V ECMO) can be considered in critically ill patient in severe pulmonary failure. However, the mobilization of patients on V-V ECMO can be challenging due to logistic and safety concerns. This study aimed to investigate whether 30 days survival was improved in patients who were mobilized during V-V ECMO support.MethodsWe conducted a retrospective cohort all-comer study that included all patients cannulated for V-V ECMO at a single center. Patients with a V-V ECMO duration below 24 h were excluded from the analysis. The patients were grouped based on the ICU mobility scale documented during V-V ECMO support. The primary endpoint was 30 days survival, and secondary endpoints included weaning from ECMO and mechanical ventilation, as well as hospital survival.ResultsA total of 343 patients were included in the study, with a median age of 56 years and 32% were female. Among them, 28% had chronic lung disease. The ICU mobilization scale ≥2 during ECMO was documented in 62/343 (18%) patients. There were no significant differences in age, gender and preexisting lung disease. Duration of ICU stay (13.1 vs. 15.6 days), time on ECMO (186 vs. 190 h) and mechanical ventilation (11.2 vs. 13.6 days) were slightly shorter in patients with ICU mobility scale &lt;2 compared to those with ≥2 (all p = 0.0001). However, patients with ICU mobilization scale ≥2 showed significantly better 30 days survival (71.0 vs. 48.0%, OR 2.6 (1.5 to 4.8), p = 0.0012) compared to those with &lt;2. In the ≥2 mobility scale group, a significantly higher number of patients were successfully weaned from the ventilator (61.3 vs. 46.6%, OR 1.8 (1.0 to 3.2), p = 0.049). A stronger correlation was observed between more intense mobilizations, such as being in a standing position (OR 5.0 (1.7 to 14.0), p = 0.0038), and higher 30 days survival.ConclusionThe findings of this study suggest that active mobilization during V-V ECMO support is associated with improved 30 days survival and successful weaning from the respirator. Incorporating mobilization as part of the therapeutic approach during ECMO support may offer potential benefits for critically ill patients.
Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer
Authors: Kumar Shreya , Mulia Grace E. , Figueiredo Marxa L. 
Published: October 2023

Introduction: Prostate cancer is the second leading cause of cancer-related death among American men. Prostate tumor cells exhibit significant tropism for the bone and once metastasis occurs, survival rates fall significantly. Current treatment options are not curative and focus on symptom management. Immunotherapies are rapidly emerging as a possible therapeutic option for a variety of cancers including prostate cancer, however, variable patient response remains a concern. Chemotherapies, like cabozantinib, can have immune-priming effects which sensitize tumors to immunotherapies. Additionally, lower doses of chemotherapy can be used in this context which can reduce patient side effects. We hypothesized that a combination of chemotherapy (cabozantinib) and immunotherapy [Interleukin-27 (IL-27)] could be used to treat bone-metastatic prostate cancer and exert pro-osteogenic effects. IL-27 is a multi-functional cytokine, which promotes immune cell recruitment to tumors, while also promoting bone repair.Methods: To test this hypothesis, in vivo experiments were performed where syngeneic C57BL/6J mice were implanted intratibially with TRAMP-C2ras-Luc cells that are able to form tumors in bone. Immunotherapy was administered in the form of intramuscular gene therapy, delivering plasmid DNA encoding a reporter gene (Lucia), and/or a therapeutic gene (IL-27). Sonoporation was used to aid gene delivery. Following immunotherapy, the animals received either cabozantinib or a vehicle control by oral gavage. Bioluminescence imaging was used to monitor tumor size over time.Results: Combinatorial therapy inhibited tumor growth and improved survival. Further, RNA sequencing was used to investigate the mechanisms involved. Microcomputed tomography and differentiation assays indicated that the combination therapy improved bone quality by enhancing osteoblast differentiation and inhibiting osteoclast differentiation.Discussion: Our conclusion is that a chemo-immunotherapy approach such as the one examined in this work has potential to emerge as a novel therapeutic strategy for treating bone-metastatic prostate cancer. This approach will enable a significant reduction in chemotherapy-associated toxicity, enhance sensitivity to immunotherapy, and improve bone quality.
Impact of paravertebral block on perioperative neurocognitive disorder: a systematic review and meta-analysis of randomized controlled trials
Authors: Wang Lu , Wang Fei , Kang Wanli , Gao Guangkuo , Liu Tao , Chen Bin , Liu Wei 
Published: October 2023

ObjectiveTo investigate whether paravertebral block reduces postoperative delirium (POD)/delayed neurocognitive recovery (DNR) in adults after major surgery with general anesthesia.MethodsFor this systematic review and meta-analysis, we searched online databases PubMed, EMBASE, CENTRAL, and Web of Science till March 19th, 2023 to examine studies which use paravertebral block (PVB) for perioperative neurocognitive disorder. Primary and secondary outcomes were identified for the incidence of perioperative neurocognitive disorder. We did not restrict the follow-up duration of the included studies. Statistical analysis was performed to calculate mean difference (MD), Odd ratios (OR) and CI between RCTs. The quality of the evidence was assessed with the Cochrane risk of bias tool. The registration number of the study in PROSPERO is CRD42023409502. PROSPERO is an international database of prospectively registered systematic reviews. Registration provides transparency in the review process and it helps counter publication bias.ResultsTotal 1,225 patients from 9 RCTs were analyzed. The incidence of POD [Odds Ratio (OR) = 0.48, 95% CI 0.32, 0.72; p = 0.0004; I2 = 0%] and DNR [OR = 0.32, 95% CI 0.13, 0.80; p = 0.01; I2 = 0%] were significantly reduced in PVB group. The analysis showed no significant differences in postoperative MMSE scores [MD = 0.50, 95% CI −2.14, 3.15; p = 0.71; I2 = 98%]. Paravertebral block analgesia reduces pain scores and/or opioid use after surgery. Additionally, blood pressure was significantly lower in the PVB group, intraoperatively [MD = −15.50, 95% CI −20.71, −10.28; p &lt; 0.001; I2 = 12%] and postoperatively [MD = −5.34, 95% CI −10.65, −0.03 p = 0.05; I2 = 36%]. Finally, PVB group had significantly shorter hospital stays [MD = −0.86, 95% CI −1.13, −0.59; p &lt; 0.001; I2 = 0%].ConclusionParavertebral block analgesia may prevent perioperative POD/DNR in patients undergoing major surgery. Further research with large sample sizes is required to confirm its effectiveness.
Peripheral vestibular loss in noise-exposed firefighters
Authors: Snapp Hillary Anne , Vanlooy Lindsey , Kuzbyt Brianna , Kolberg Courtney , Laffitte-Lopez Denise , Rajguru Suhrud 
Published: October 2023

IntroductionOccupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP).MethodsA cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold.ResultscVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway.DiscussionIn the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.
Case Report: Resolution of high grade anal squamous intraepithelial lesion with antibiotics proposes a new role for syphilitic infection in potentiation of HPV-associated ASCC
Authors: Ranabhotu A. , Habibian N. , Patel B. , Farrell E. , Do J. , Sedghi S. , Sedghi L. 
Published: October 2023

IntroductionHuman Papillomavirus (HPV) is the primary risk factor for the development of anal intraepithelial neoplasia (AIN) and is a leading risk factor for anogenital squamous cell carcinoma (ASCC). Despite common shared risk factors for both HPV and syphilis, co-infection is not well documented, and the role of syphilitic infection in HPV-associated AIN and ASCC potentiation is not defined.Case description/methodsA 72-year-old single male presented with complaints of mild rectal pain and intermittent rectal bleeding. A flexible sigmoidoscopy was performed, and a firm 4.5cm x 3cm perianal mass was detected and superficially biopsied. Pathology findings demonstrated evidence of a high grade squamous intraepithelial lesion (HGSIL, AIN II/III/AIS) with viral cytopathic effect, consistent with HPV infection. Much of the biopsied lesion showed acanthotic squamous mucosa with intraepithelial neutrophils and abundant submucosal plasma cells, suggesting possible syphilitic involvement. Subsequent immunohistochemical staining for p16 as a surrogate marker for HPV was positive, as was an immunohistochemical stain for spirochetes, supportive of co-infection with Treponema pallidum pallidum (T. pallidum), the causative agent in venereal syphilis. The patient was referred to an infectious disease specialist for syphilitic infection and was treated with penicillin with surprisingly complete resolution of the lesion. EUAs were performed 2- and 3-months following treatment without lesion recurrence. However, one year following diagnosis, a flexible sigmoidoscopy revealed a 5 mm recurrent HPV-related low-grade AIN 1 lesion at the dentate line.DiscussionResolution of the lesion by antibiotic treatment for syphilitic infection suggested that co-infection by T. pallidum may potentiate HPV-associated squamous cell carcinoma based on histological findings. Findings from this case, as well as a review of bacterial involvement and potentiation in various cancers, are reviewed here. Such findings offer new insight regarding the role of STI-associated bacteria and HPV co-infection in the establishment of AIN and may additionally propose new treatment modalities for ASCC.
Vulvar squamous intraepithelial neoplasia epithelial thickness in hairy and non-hairy sites: a single center experience from China
Authors: Xiao Jingjing , Chen Ziren , Xiao Yinping , Sui Long , Wang Chao , Cong Qing 
Published: October 2023

IntroductionA large-sample study focusing on VIN lesions of a more precise thickness is needed to help guide clinical treatment. This study aimed to investigate the depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for laser surgery.MethodsThe study retrospectively enrolled and analyzed the clinical characteristics of VIN patients in the obstetrics and gynecology department of a university hospital between January 1, 2019 and December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN1) and 285 women with high-grade VIN (VIN2/3).ResultsThe study included 1,139 (80%) VIN1 and 335 (20%) VIN2/3 cases. The VIN1 and VIN2/3 groups showed a significant difference in human papillomavirus infection (P&lt;0.01) but not in cytology (P = 0.499). Most (89.90%, 1,325) cases occurred in one area of the vulva, whereas 10.11% were multifocal. VIN commonly occurred on the posterior fourchette (76.85%), labia majora (11.61%), and labia minora (9.92%). The VIN2/3 group reported a significantly higher positive rate for concurrent cervical and vaginal intraepithelial neoplasia (160 of 285) than the VIN1 group (321 of 953) (P=0.000). The involved epithelial thicknesses in VIN2/3 and VIN1 were 0.69 ± 0.44 and 0.49 ± 0.23 mm, respectively, both of which were greater than the corresponding noninvolved epithelial thickness (0.31 ± 0.19 and 0.32 ± 0.10 mm, P&lt;0.001 and P&lt;0.001, respectively). In cases of appendage involvement, the VIN thickness was 1.98 ± 0.64 mm.ConclusionsVIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. However, for lesions extending onto hairy areas, the thickness was approximately 3 mm, leading to the destruction of involved skin appendages.