bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Effectiveness of Focused Shockwave Therapy and Radial Wave Therapy for Erectile Dysfunction: A Two Centre Prospective Cohort Study
Authors: Bayar Goksel , Ofluoglu Yilmaz , Yildirim Caglar , Basmaci Ismail , Yavuz Abdulmecit
Published: October 2024

Background
Focused shockwave therapy (fSWT) has now taken its place in the algorithm for the treatment of vascular erectile dysfunction (ED) in current guidelines. Radial wave therapy (rWT) has started to be applied with the same indication in recent years and positive results have been reported.
Objective
To compare the long-term effectiveness of focused shockwave therapy fSWT and radial wave therapy rWT in ED.
Methods
A two-center study enrolled 200 patients aged 40 to 70 years with ED complaints. Patients were non-randomly allocated to either fSWT or rWT groups based on the clinic they visited. Pre- and post-treatment International Index of Erectile Function (IIEF) scores were compared, minimal clinically important differences (MCIDs) were calculated and Sexual Encounter Profile-2 (SEP-2) was recorded.
Results
After 3 months, the mean IIEF score for patients in the fSWT group was significantly higher compared to the baseline (13 ± 2.9 vs. 20.4 ± 4.7, p < 0.001), and the same trend was observed at 1 year (13 ± 2.9 vs. 18.1 ± 4.9, p < 0.001). Similarly, in the rWT group, the mean IIEF score was significantly higher at 3 months (13.1 ± 3 vs. 22.8 ± 4.6, p < 0.001) and 1 year (13.1 ± 3 vs. 19.4 ± 4.9, p < 0.001) compared to the baseline. However, there was no significant difference in the mean IIEF score changes between the two groups at both 3 months and 1 year. The proportion of patients giving a positive response to the SEP-2 question was 81% at 3 months and 63.2% at 1 year in the fSWT group, and 88.9% at 3 months and 71.6% at 1 year in the rWT group, with no significant difference between the groups.
Conclusions
Both fSWT and rWT are effective treatments for vascular-related ED, showing comparable efficacy in improving IIEF scores. The potential for periodic applications and longer-term effects warrants further investigation through extended follow-up studies.
The Gut Microbiota Genus Blautia is Associated with Skeletal Muscle Mass Reduction in Community-Dwelling Older Japanese Adults: The Wakayama Study
Authors: Sakaguchi Masato , Miyai Nobuyuki , Zhang Yan , Sakamoto Yukiko , Terada Kazufumi , Utsumi Miyoko , Takeshita Tatsuya , Arita Mikio
Published: October 2024

Purpose: This cross-sectional study examined the gut microbiota species associated with skeletal muscle mass reduction in a community-based sample of older Japanese adults.
Methods: The study included 744 participants aged 65–89 years (mean age, 73 years) with no history of treatment for colorectal, chronic kidney, or liver diseases. Bioelectrical impedance analysis was performed to estimate the appendicular skeletal muscle mass (ASM) of each participant. The gut microbiota composition was assessed using next-generation sequencing targeting the V3-V4 regions of the prokaryotic 16S rRNA genes. A self-administered questionnaire was used to evaluate daily living habits, including food intake associated with maintaining the gut microbiota.
Results: Among the participants, those with reduced muscle mass (defined as an ASM index of less than 4.4 kg/m² for men and 3.7 kg/m² for women) had significantly higher levels of the genus Blautia when compared with those with normal muscle mass (P=0.009). Logistic regression analysis revealed that the association between the genus Blautia and skeletal muscle mass remained significant even after adjusting for multiple confounding factors (P=0.012). Additionally, an increase in the genus Blautia was positively associated with excessive alcohol consumption (≥ 20 g/day, β=0.125, P=0.002) and negatively associated with regular yogurt intake (≥ 1 time/week, β=-0.101, P=0.010), independent of other lifestyle and dietary factors.
Conclusion: Elevated levels of the genus Blautia were associated with reduced skeletal muscle mass in older Japanese adults, suggesting that improving the gut microbiota may be a potential approach to preserving muscle mass among this population.
Pterygomandibular raphe invasion as a prognostic factor in squamous cell carcinoma of the buccal mucosa
Authors: Yoshida Ryoji , Lin Riu , Yamana Keisuke , Obayashi Takeshi , Takeshita Hisashi , Kawahara Kenta , Hirayama Masatoshi , Takahashi Nozomu , Hirosue Akiyuki , Nakayama Hideki
Published: October 2024

This retrospective study assessed the prognostic significance of pterygomandibular raphe (PMR) invasion in resectable squamous cell carcinoma of the buccal mucosa (SCCBM). We included 82 patients with SCCBM who underwent radical resection at Kumamoto University Hospital between 2000 and 2017. Patients were categorized into three groups based on PMR invasion patterns: noncontact, contact, and invasion. The relationship between PMR invasion and clinicopathological characteristics was analyzed using Fisher’s exact test. The Kaplan–Meier method, log-rank test, and Cox regression model were employed for survival analysis. Results indicated that contact or invasion into the PMR was significantly associated with advanced clinical T and N stages, clinical stage, endophytic growth pattern, high-grade invasion pattern, poor tumor differentiation, extranodal extension, and distant metastasis. Patients with PMR invasion experienced a significantly higher proportion of recurrences in the buccal, subcutaneous, mandibular, and masticatory spaces. Univariate analysis indicated that PMR invasion by contact or invasion type SCCBM was a predictor for worse local control rate, disease-free survival, and overall survival, while multivariate analysis revealed that it was an independent worse prognostic factor for overall survival. Thus, PMR invasion is a key prognostic factor in resectable SCCBM.
Integrating Radiomics Features and CT Semantic Characteristics for Predicting Visceral Pleural Invasion in clinical stage Ia peripheral Lung Adenocarcinoma
Authors: Zhao Yunqing , Ye Zhaoxiang , yan Qingna , sun Haoran , Zhao Fengnian
Published: October 2024

Objectives
The aim of this study was to non-invasively predict the visceral pleural invasion (VPI) of peripheral lung adenocarcinoma (LA) highly associated with pleura of clinical stage Ia based on preoperative chest computed tomography (CT) scanning.
Methods
A total of 537 patients diagnosed with clinical stage Ia LA underwent resection and were stratified into training and external validation cohorts at a ratio of 7:3. Radiomics features were extracted using PyRadiomics software following tumor lesion segmentation and were subsequently filtered through spearman correlation analysis, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator regression analysis. Univariate and multivariable logistic regression analyses were conducted to identify independent predictors. A predictive model was established with visual nomogram and external validation, and evaluated in terms of area under the receiver operating characteristic curve (AUC).
Results
The independent predictors of VPI were identified: pleural attachment (p < 0.001), pleural contact angle (p = 0.018) and Rad-score (p < 0.001). The combined model showed good calibration with an AUC of 0.822 (95% confidence intervals (CI): 0.785, 0.869), compared with 0.719 (95% CI: 0.677, 0.760; DeLong’s test p < 0.001) when radiomics was used alone. For validation group, the accuracy of combined prediction model was reasonable with an AUC of 0.785 (95% CI: 0.742, 0.821).
Conclusion
Our predictive model, which integrated radiomics features of primary tumors and peritumoral CT semantic characteristics, offers a non-invasive method for evaluating VPI in patients with clinical stage Ia LA. Additionally, it provides prognostic information and supports surgeons in making more personalized treatment decisions.
Associations Between Maternal Abortion History and Neonatal Outcome among Very Preterm Infants：a multicenter cohort study
Authors: Yang Min , Yang Jie , Wang Dianna , Dai Jiale , Fan Xiaobo , Cao Yun , Zhou Wenhao , Lee Shoo K , Wang Jimei , Hu Liyuan
Published: October 2024

Background
It is unclear whether there is an association between maternal abortion history and neonatal outcomes of singleton very preterm infants (VPIs). We assess the association between maternal abortion history and neonatal outcome of VPIs in China.
Methods
All first parity singleton VPIs born at < 32 weeks gestational age (GA) who were admitted to neonatal intensive care units (NICU) participating in the Chinese Neonatal Network (CHNN) from 2019 to 2021 were included in the study. Multivariable logistic regression models were constructed to compare neonatal outcomes among infants with different maternal abortion histories after adjusting for confounders.
Results
A total of 7256 VPIs were included in this analysis. Overall, 3133 (43.2%) infants had positive maternal abortion history. The incidence of mortality or any major morbidity including respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), intraventricular haemorrhage (IVH), IVH stage 3 or 4, moderate or severe bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), ROP stage 3, 4, or 5 tended to increase significantly with increasing number of maternal abortion histories from non-abortion group to ≥2 abortions group. Multivariable analysis showed that maternal abortion history was significantly associated with higher risks of mortality or any major morbidity (adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.03–1.29), RDS (aOR 1.22, 95%CI 1.08–1.38), IVH (aOR 1.17, 95% CI 1.05–1.31), and IVH stage 3 or 4 (aOR 1.27, 95% CI 1.01–1.59). Risk increased with the number of abortions. VPIs of mothers with two or more abortions had the highest risk of mortality or any major morbidity (aOR 1.18, 95% CI 1.02–1.36), RDS (aOR 1.35, 95% CI 1.18–1.56), IVH (aOR 1.23, 95% CI 1.07–1.43) and moderate or severe BPD (aOR 1.17, 95% CI 1.01–1.36), compared to the non-abortion group.
Conclusions
In China, VPIs born to mothers with previous abortion history may have a greater risk of adverse outcomes. Based on the potential impact of maternal abortion history on newborns, it is necessary to provide additional information on related risks during antenatal counseling for these mothers.
Elevation of lipoprotein(a) and PCSK9 serum plasma concentration among patients with angiogram-proven premature coronary artery disease in an Asian Cohort
Authors: Zulkapli Rahayu , Nawawi Hapizah , Muid Suhaila Abd , Wang Seok Mui , Ra Ahmad Bakhtiar Md , Ibrahim Khairul Shafiq
Published: October 2024

Coronary artery disease (CAD) has been associated with elevated Lp(a) levels, yet the underlying mechanism by which Lp(a) mediates atherogenesis and inflammation is still incompletely understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) known to be during the inflammatory process, thus a potential relationship between Lp(a) and PCSK9 could be established. This study aimed to investigate the correlation and association between Lp (a) and PCSK9 in the angioproven-premature CAD (AP-pCAD) subjects with and without FH. Patients were recruited from Cardiology and Specialist Lipid Clinics were grouped into + pCAD + FH (n = 70), +pCAD -FH (n = 65), and -CAD-FH (G3; n = 69). FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria. Lp(a) and PCSK9 levels were measured using an automated chemistry analyser and ELISA, respectively. Both were higher in + pCAD + FH [27.2 (13.2–72.2), 431.4 (178.0-1008.0)] and + pCAD -FH [34.7 (12.7-100.9), 471.4 (333.1–1188.0] compared to G3 [7.5 (7.0-14.7), 389.7 (147.1-566.2)]. In conclusion, Lp(a) and PCSK9 levels were significantly higher in pCAD compared to G3-normal control (NC) group, regardless the FH clinical diagnosis. A significant correlation was found in all pCAD and NC groups. We suggested that PCSK9 concentration is correlated with Lp(a) levels in pCAD and NC groups, indicating its potential of becoming a CAD predictor.
Exploring the Mechanism of Macleaya cordata (Willd) R. Br. Against Breast Cancer by Network Pharmacology and Molecular Docking
Authors: Zhang Lei , Huang Jing , Peng Yulong , Yin Su , Cao Yang , Nan Kai
Published: October 2024

Macleaya cordata (Willd) R. Br. (M. cordata) has widely reported antitumor activity, while the underlying mechanism of M. cordata anti-breast cancer (BC) still remains unclear. The compounds of M. cordata were collected from previous researches and screened by drug-likeness rules to identify bioactive compounds. The targets were obtained from MalaCards, Online Mendelian Inheritance in Man, and SwissTargetPrediction database, then overlapped to get intersections as potential anti-BC targets of M. cordata. After topological analysis of the protein-protein interaction network, the correlation analysis of gene expression and patient pathological stage and survival, respectively, was performed, and 4 pivotal targets were obtained. Four bioactive compounds of M. cordata (6-cyanodihydrogensanguinarine, Corysamine, Oxychelirubine, and Berberrubine) had strong binding efficiency with the 4 pivotal genes after molecular docking analysis. The current study demonstrated that M. cordata acts against BC through multiple targets and pathways that may guide further studies on M. cordata anti-BC effects.
Fellowship by the Numbers: Surgical Fellowship Applications in the United States
Authors: Turlington Margaret Sundel , Campbell Brady A. , Cahn Matthew , McClure Megan , Kavic Stephen M.
Published: October 2024

Purpose:
The majority of residents pursue fellowship following training in general surgery, especially at academic medical centers. However, there is no singular body that oversees fellowship, and many aspects of fellowship remain speculative, including application and admissions. Our aim was to define the known statistics around surgical fellowships.
Methods:
We performed a retrospective analysis of publicly available data from the National Residency Match Program (NRMP), the Fellowship Council, the SF Match, and the American Council on Graduate Medical Education Data Resource Book for 2014–2023. We included data on colorectal surgery, surgical critical care, minimally invasive surgery, surgical oncology, pediatric surgery, plastic surgery, thoracic, transplant, and vascular surgery fellowships. We did not include burn fellowship, pediatric critical care surgery, or research fellowships.
Results
66% of US surgical residents pursue fellowship, which has been stable over the past decade. The largest fellowships are critical care, minimally invasive, vascular, and colorectal surgery. There is a very high match rate among critical care, surgical oncology, vascular, and transplant surgery for US trainees, while pediatric surgery consistently has the lowest match rate. US trainees are more likely to match into fellowship than non-US graduates.
Conclusions
This study provides a comprehensive snapshot of surgical fellowships in the United States. Two-thirds of surgery residents pursue fellowship, and the likelihood of matching varies substantially between specialties. These results can help inform national workforce planning and may be valuable to current residents in their fellowship application process.
Transparent, flexible graphene-ITO-based neural microelectrodes for simultaneous electrophysiology recording and calcium imaging of intracortical neural activity in freely moving mice
Authors: Pei Weihua , Yuan Miao , Li Fei , Xue Feng , Wang Yang , Tang Rongyu , Wang Yijun , Bi Guo-Qiang
Published: October 2024

To understand of the complex dynamics of neural activity in the brain across various temporal and spatial scales, it is crucial to record intracortical multimodal neural activity by combining electrophysiological recording and calcium imaging techniques. This poses significant constraints on the geometrical, mechanical and optical properties of the electrodes. Here, transparent flexible graphene-ITO-based neural microelectrodes with small feature sizes are developed and validated for simultaneous electrophysiology recording and calcium imaging in the hippocampus of freely moving mice. A micro-etching technique and an oxygen plasma pre-treating method are introduced to facilitate large-area graphene transfer and establish stable low-impedance contacts between graphene and metals, leading to the batch production of high-quality microelectrodes with interconnect widths of 10 µm and recording sites diameters of 20 µm. These electrodes exhibit appropriate impedance and sufficient transparency in the field pf view, enabling simultaneous recording of intracortical local field potentials and even action potentials along with calcium imaging in freely moving mice. Both types of electrophysiological signals are found to correlate with calcium activity. This proof-of-concept work demonstrates that transparent flexible graphene-ITO-based neural microelectrodes are promising tools for multimodal neuroscience research.
Projections of Greenhouse Heating and Ventilation Requirements in the New Valley Under Climate Change Scenarios
Authors: MEDANY MAHMOUD , Radwan Ghada , Zaki Milad H.
Published: October 2024

Egyptian greenhouse megaproject is expanding all over the country in the recent years. Vegetable optimum growth under greenhouses requires temperature range from 15–32°C. The latest assessment report of the Intergovernmental Pannel for Climate Change revealed different temperature increases under different scenarios ranging from 2.6 to 8.5 for different global regions, including North Africa and Middle East, till the end of the decade. This study was conducted in Kharga Oasis, the New Valley Governorate, in the west south Egypt, in order to investigate the heat requirements and number of mechanical ventilation hours needed for vegetable production under greenhouses during the reference year of 2023–2024, compared to historical period of 1995–2014, and under climate change projections. Four future scenarios were used: SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) according to the IPCC sixth Assessment Report, with four projection intervals: 2020–2039, 2040–2059, 2060–2079, and 2080–2099. Hourly data was used for the estimation of heat requirements (kwh) when temperatures were lower than 15°C, in a greenhouse of 8.5m width, and 40m length and for the number of hours needed for ventilation if temperatures exceed 28, 30, 23 and 35°C. The results indicated that total heating requirements (kilo calory, kCal) decreased gradually from the actual estimated (2023–2024) from 755.1 (≈ 0.88 kWh) to 477.3, (≈ 0.55 kWh) 282.1 (≈ 0.33 kWh), 134.6 (≈ 0.16 kWh), and 66.1 (≈ 0.07 kWh) kCal by the years 2080–2099 under the worst-case scenario of SSP5-8.5, respectively. Seasonally, winter months (December, January and February) were almost the months that required all heating, while the rest of the year minimum temperatures were higher than the 15°C set point. Ventilation hours were decreased from 2771, 2446, 2018, and 1495 hours/year by increasing set point temperatures from 28, to 30, 32, and 35°C, for the actual estimated period (2023/2024), respectively. As for the projected time intervals, the number of hours increased to reach 3564 hours/year under the SSP5-8.5 scenario for the projected time intervals 2080–2099. The lowest projected number of hours values for temperature set point of 32°C were obtained under the ss91-2.6 scenario (1707 − 1495 hours), while the highest values were obtained under the pessimistic scenario (SSP5-8.5) ranging from 1709 to 2341 hours/year for the whole projection intervals towards the end of the century. Ventilation hours required were distributed in a descending order among summer, autumn and spring. These results indicate the need for vital attention in constructing new greenhouses, and to find the best cultivation dates for coping with climate change temperature rise till the end of the century.
Synchronous Management of Urethral Stricture Disease and Penile Prosthesis Implantation: A Case Series
Authors: Du Comb William , Maremanda Ankith , Alshak Mark , Nalwa Harjit , Able Corey , Burnett Arthur
Published: October 2024

There is currently limited data to describe managing a urethral stricture identified while attempting penile prosthesis placement. This study reports our management of urethral strictures during penile prosthesis placement and proposes a guideline for this event. A retrospective analysis was performed on patients who underwent penile prosthesis implantation and had incidentally found urethral stricture disease from 2009 to 2023. Cases that proceeded were classified as “completed,” while cases that could not proceed were classified as “aborted.” Successful management was defined as the absence of complications requiring explantation within 90 days of the procedure. Twenty-four cases were identified. Of these twenty-four patients, eighteen had completed procedures, while six had their procedures aborted. Within 90 days after the procedure, one patient presented with urinary retention. No patients had penile prosthesis infections within 90 days. Of the six “aborted” patients, five had strictures greater than 2 cm in length with urethral lumens between 8-10F. One patient had an obliterated urethra; three patients underwent urethroplasty; one patient underwent urethral dilation and suprapubic tube placement; and two patients underwent a direct vision internal urethrotomy. This retrospective study surrounding synchronous penile prosthesis implantation and urethral stricture disease management yielded high success and low complication rates.
Assessing the readiness and feasibility to implement a model of care for spine disorders and related disability in Cross Lake, an Indigenous community in northern Manitoba, Canada: A research protocol
Authors: Bussières André , Passmore Steven , Kopansky-Giles Deborah , Tavares Patricia , Ward Jennifer , Ladwig Jacqueline , Glazebrook Cheryl , Mior Silvano , Atkinson-Graham Melissa , Moss Jean , Robak Nicole , Broeckelmann Elena , Monias David A , Mckay Donnie Z , Hamilton Helga , Scott Muriel , Smolinski Randall , Hurwitz Eric L , Woolf Anthony D , Haldeman Scott
Published: October 2024

Background
Since the 1990s, spine disorders have remained the leading cause of global disability, disproportionately affecting economically marginalized individuals, rural populations, women, and older people. Back pain related disability is projected to increase the most in remote regions where lifestyle and work are increasingly sedentary, yet resources and access to comprehensive healthcare is generally limited. To help tackle this worldwide health problem, World Spine Care Canada, and the Global Spine Care Initiative (GSCI) launched a four-phase project aiming to address the profound gap between evidence-based spine care and routine care delivered to people with spine symptoms or concerns in communities that are medically underserved. Phase 1 conclusions and recommendations led to the development of a model of care that included a triaging system and spine care pathways that could be implemented and scaled in underserved communities around the world.
Methods
The current research protocol describes a site-specific customization and pre-implementation study (Phase 2), as well as a feasibility study (Phase 3) to be conducted in Cross Lake, an Indigenous community in northern Manitoba, Canada. Design: Observational pre-post design using a participatory mixed-methods approach. Relationship building with the community established through regular site visits will enable pre- and post-implementation data collection about the model of spine care and provisionally selected implementation strategies using a community health survey, chart reviews, qualitative interviews, and adoption surveys with key partners at the meso (community leaders) and micro (clinicians, patients, community residents) levels. Recruitment started in March 2023 and will end in March 2026. Surveys will be analyzed descriptively and interviews thematically. Findings will inform co-tailoring of implementation support strategies with project partners prior to evaluating the feasibility of the new spine care program.
Discussion
Knowledge generated from this study will provide essential guidance for scaling up, sustainability and impact (Phase 4) in other northern Canada regions and sites around the globe. It is hoped that implementing the GSCI model of care in Cross Lake will help to reduce the burden of spine problems and related healthcare costs for the local community, and serve as a scalable model for programs in other settings.
Efficacy and Safety of Vaginal Suppositories Containing Combination of Natamycin and Lactulose in Treatment of Vulvovaginal Candidiasis: International, Randomized, Controlled, Superiority Clinical Trial (Combination of Natamycin and Lactulose for Treatment of Vulvovaginal Candidiasis)
Authors: Volkova Oksana. N. , Amel'chenko Elena V. , Makeeva Oksana V. , Tolmachev Sergey A. , Lesovaya Ekaterina A. , Zacharia Lefteris , Dikovskiy Alexander V.
Published: October 2024

Background: The study aimed to assess the efficacy and safety of Natamycin + Lactulose vaginal suppositories (100 mg natamycin and 300 mg lactulose) (AVVA RUS JSC, Russia) in adult females with vulvovaginal candidiasis.
Methods and Results: An international, randomized, controlled, assessor-blinded clinical trial enrolled 218 females who were randomized into three groups: Natamycin + Lactulose (92 patients), Lactulose (36 patients), and Pimafucin® (90 patients). The study drug and comparator drugs had an identical dosing regimen (one suppository intravaginally once daily at bedtime for six days). The study involved four visits to the study site with the examination at Visits 2 and 3.
Fixed combination of Natamycin + Lactulose was superior to both comparator drugs for the primary efficacy endpoint defined as percentage of patients who achieved a clinical recovery: the absence of symptoms of vulvovaginal candidiasis. At Visit 2, clinical recovery was reported in 81.6% of females in Natamycin + Lactulose group compared to 42.9% in Lactulose group and 62.3% of patients in Pimafucin group. The difference in proportions was 38.8% and 18.4%. In Natamycin + Lactulose group, microscopic recovery (Visit 2) was observed in 75.9% of patients at Visit 2 and in 90.8% of patients at Visit 3. In Lactulose group, 45.7% and 74.3% subjects responded positively at Visits 2 and 3. In Pimafucin group, 71.3% and 88.5% of patients showed microscopic recovery at Visits 2 and 3. For the microscopic recovery, no differences were reported between Natamycin + Lactulose and Pimafucin groups at both visits. At Visit 3, the number of vaginal lactobacilli was significantly higher in Natamycin + Lactulose group. In females with low baseline values of vaginal lactobacilli, the study combination increased the vaginal levels of lactobacilli to the reference values in 15.4% of patients at Visit 2, and in 20.9% of patients at Visit 3.
Conclusions: The fixed combination Natamycin + Lactulose 100 mg + 300 mg vaginal suppositories (AVVA RUS JSC, Russia) demonstrated superior efficacy compared to 1) Pimafucin 100 mg and 2) Lactulose 300 mg vaginal suppositories in adult females with vulvovaginal candidiasis.
Trial registration: NCT06411314, retrospectively registered on May, the 13th, 2024.
Efficacy and Safety of Chemoradiation with Cisplatin plus Capecitabine in Localized Squamous Cell Anal Cancer
Authors: Dornellas Abraão , Bonadio Renata , Moraes Priscila , Galhera Denis , Victor Carolina , Chen Andre , Muratori Carolina , Ortega Cinthia , Alves Henrique , Ibrahim Karim , Nahas Caio , Marques Carlos Frederico , Alban Luciana , Braghiroli Maria Ignes , Hoff Paulo Marcelo , Moniz Camila
Published: October 2024

Background
Localized Squamous Cell Anal Cancer (SCCAC) is a rare disease. The standard of care treatment with curative intent is chemoradiation (CRT) with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-Fluoracil (5-FU). Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are frequently unavailable in underdeveloped countries. CCDP and capecitabine are widely available, but there is no prospective data about the feasibility and efficacy of this combination in a definitive SCCAC CRT setting.
Methods
A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP 60mg/m2 D1 and D29 plus Capecitabine 825mg/m2 BID in a population without MMC and infusional pump access. Eligible patients (pts) had T2-4, N0-3, and M0 disease candidates for a full curative CRT regimen. The study data were prospectively collected using REDCap. The primary endpoint was the response by RECIST v.1.1 at 24 weeks(w). The secondary endpoints included toxicity by CTCAE v.5.0, PFS, and OS.
Results
We enrolled 40 consecutive pts between Aug/2019-Dec/2022 in a tertiary cancer center in Brazil. The median age was 61.6y, the majority were stage III (n = 31, 77.5%) and ECOG 1 (n = 20, 50%). HIV + serology was observed in 11 pts (27,5%). All patients received CRT, with a median dose of 54Gy in the primary tumor and 45Gy in the elective nodes. At 8w, 35% (n = 14) had a complete response (CR), 50% (n = 20) partial response (PR), and 2.5% (n = 1) progressive disease (PD). Considering the 35 participants evaluable for response at 24 weeks months by RECIST v.1.1, the disease control rate was 88.5% (n = 31). CR was observed in 47,5% (n = 19), PR in 20% (n = 8), and PD in 12,5% (n = 5). 11 pts had disease recurrence, and six died. The 1y estimated OS was 94.7% (IC95%: 80.7–98.6%), and 1y estimated PFS was 75.3% (IC95%:57.8–86.3%). Colostomy-free survival at one year was 89.6% (IC95%: 74.7–95.9%). Regarding toxicities, any grade 3/4 toxicity was present in 45% (n = 18) being the main G3/4 clinical toxicity radiodermatitis.
Conclusions
The CRT regimen with C + CDDP represents an alternative treatment for localized anal canal tumors in a population that does not have access to MMC and 5-FU infusion pumps. Further studies in this population are encouraged to confirm these findings.
The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and bone mineral density in US adults: NHANES (2011-2018)
Authors: Sun Zhengyu , Yue Yong , Li Pengcheng
Published: October 2024

Background
The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) represents a novel lipid marker. This study investigated the association between NHHR and lumbar bone mineral density (BMD) in the general American population.
Methods
Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018 were used in this study, including 10,879 participants aged 20–59 years. To investigate the relationship between NHHR and lumbar BMD, we employed multivariate linear regression models along with stratified analyses. Additionally, we applied fitted smoothing curves and threshold effect analyses to explore the nonlinear association between NHHR and lumbar BMD.
Results
After adjusting for covariates, weighted multivariable linear regression models indicated a significant negative association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and lumbar bone mineral density (BMD) (β = -0.006, 95% CI: -0.008 to -0.003, P < 0.001). Stratified subgroup analyses based on age, gender, race, BMI, hypertension, and diabetes consistently demonstrated this inverse relationship in males (β = -0.005, 95% CI: -0.008 to -0.002, P = 0.002) and females (β = -0.007, 95% CI: -0.011 to -0.003, P < 0.001); non-Hispanic whites (β = -0.005, 95% CI: -0.009 to -0.001, P = 0.015), non-Hispanic blacks (β = -0.010, 95% CI: -0.017 to -0.004, P = 0.003), and other races (β = -0.007, 95% CI: -0.011 to -0.003, P = 0.001); participants aged 20–29 years (β = -0.006, 95% CI: -0.011 to -0.001, P = 0.022) and 40–49 years (β = -0.008, 95% CI: -0.013 to -0.003, P < 0.001); individuals with a BMI < 25 (β = -0.008, 95% CI: -0.014 to -0.002, P = 0.010) and those with a BMI between 25 and 30 (β = -0.011, 95% CI: -0.015 to -0.007, P < 0.001). For the total cohort, individuals of other races, and participants aged 30–39 years, a nonlinear relationship was examined with inflection points identified at NHHR values of 4.29, 5.26, and 2.91, respectively.
Conclusions
For US adults aged 20 to 59, our research identified an inverse relationship between the NHHR and lumbar BMD. This association was observed across the general cohort, individuals of other races, and participants aged 30–39 years, demonstrating a nonlinear relationship with inflection points at 4.29, 5.26, and 2.91, respectively. Consequently, NHHR could serve as a sensitive biomarker for the prevention of osteoporosis or osteopenia.
The diagnostic value of serum C-reactive protein/high-density lipoprotein in microvascular angina
Authors: Zhao Wenxin , Wang Lida , Cai Yongxu , Zhao Xianfeng , Li Zhongyan
Published: October 2024

Objective This study aimed to explore the relation ship between the serum ratio of C-reactive protein (CRP) to high density lip opro tein cholesterol (HDL-C) with microvascular angina(MVA).It also aimed to evaluate the predictive value of serum CRP /HDL-C in relation to MVA.
Methods The observation group consisted of 70 patients diagnosed with MVA ,while the control group included 68 patients with normal or minimal (< 50%) stenosis on coronary angiography, negative ECG exercise test and normal coronary blood flow randomly selected using a random number table method.Serum CRP,HCY,HDL-C and other relevant parameters were measured in both groups, with CRP /HDL-C calculated.Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed to identify independent risk factors for microvascular angina.
Results CRP/HDL-C levels were significantly elevated in MVA patients with statistical significance (P < 0.001).The parameterswas identified as independent risk factor for predicting MVA occurrence.The results of ROC analysis indicated that CRP /HDL-C showed high predictive value for diagnosing MVA .The CRP/HDL-C had a higher area under the curve (AUC) for diagnosing microvascular angina compared to individual parameters ,with a statisticallysignificantdifference(P<0.05).
Conclusions Elevated CRP /HDL-C levels can serve as positive predictors for diagnosing MVA.The parameters can enhance diagnostic accuracy and aid in the early identification of MVA patients..
Integrating human plasma proteomes with genome-wide association data implicates novel proteins and drug targets for Rheumatoid arthritis
Authors: Ke Xin , Yao Shi , Wu Hao , Zheng Xi , Liu Tian-Yue , Yang Feng-Fan , Li Yi-Fan , Zhang Kui , Zheng Zhao-Hui , Zhu Ping
Published: October 2024

Background
Genome-wide association studies (GWAS) have uncovered over 100 loci associated with Rheumatoid arthritis (RA) risk. However, how these loci contribute to RA risk remains largely unknown, which has hampered the development of new therapeutics. To identify genes contributing to RA risk through their effects on protein abundance, we conducted the first large-scale proteome-wide association study (PWAS) by integrating the largest up-to-date RA GWAS results with human plasma proteomes.
Methods
The PWAS was perform using RA GWAS summary statistics from discovery (22,350 RA cases and 74,823 controls) and replication (31,313 RA cases and 995,377 controls) cohorts, by leveraging precomputed protein expression weights generated from ARIC (N = 7,213) and INTERVAL (N = 3,301) studies. Then, Mendelian randomization (MR) and colocalization analyses were employed to investigate causal relationships between PWAS proteins and RA. Druggable targets exploration were finally conducted to prioritize potential therapeutic targets for RA.
Results
We identified 21 genes whose genetically regulated protein abundances were associated with RA risk. Of note, 10 genes were potentially causal and were prioritized as candidate RA genes. Among the 10 causal genes, six genes (OLFML3, PAM, ICOSLG, FCRL3, ERAP2, IL6R) were also associated to RA at transcriptome level, including the three novel genes (ICOSLG, FCRL3, ERAP2) that were not implicated in the original GWAS, which were regarded as novel candidate genes for RA. Druggable targets exploration identified 120 drug-gene interactions involving in 7 causal PWAS genes, including seven drugs or compounds targeting novel PWAS gene ERAP2 and ICOSLG, which possesses superior anti-inflammatory and anti-rheumatic activity in autoimmune diseases, hence might be candidates for treating RA.
Conclusions
Our results provide novel insights into RA pathogenesis and promising targets for further mechanistic investigations and drug development of RA.
Solifenacin versus Tolterodine in Catheter-Related Bladder Spasms following Prostatectomy; A Randomized Triple-blind Study.
Authors: Oyelowo Nasir , Nkemdilim Oyetola Okonji Ifeyinwa , Sudi Abdullahi , Khalid Abdullahi , Musliu Adetola Tolani , Agbo Christian Agbo , Muhammed Salihu Muhammed , Ahmed Muhammed
Published: October 2024

Background: Bladder spasms are common during the immediate postoperative period while the urethral catheter is insitu following prostatectomy. This often presents in the form of urgency, intense suprapubic pain, increased bleeding, and pericatheter leakage of urine. This is due to involuntary contractions of detrusor muscle stimulated by the bladder mucosa's irritation by the urethral catheter's ballon in situ. These bladder spasms post-prostatectomy can be inhibited using selective antimuscarinics such as Solifenacin and tolterodine. Both have been found efficacious in relieving patients with overactive bladder syndrome and urinary incontinence. The efficacy and tolerability of these agents in post-prostatectomy patients with bladder spasms were reviewed to guide treatment decisions.
Methods: Patients scheduled for prostatectomy for BPH from March 2022 to February 2023 were studied. Patients who had bladder spasms post-prostatectomy were allocated using simple randomization into two different groups; Group A received 10mg of Solifenacin daily and Group B 4mg of Tolterodine daily. Treatment was for a week from the onset of symptoms. The primary outcome measure was the resolution of spasms within the treatment period. Changes in pain scores were assessed using the visual analog scale, and the frequency of side effects of the therapy were secondary outcomes.
Results: A total of 126 had prostatectomy during the study period and 72(60%) of the patients had bladder spasms following the procedure and were randomized into both treatment arms. The age of the patients, approach to surgery, and clinical characteristics of the patients were similar in both groups and no statistically significant difference was seen. Complete resolution of symptoms was seen in 68% of patients in the Solifenacin group while in 59% of patients in the Tolterodine group. This was significant with p.value=0.001. The changes in mean pain scores were statistically significant in the two groups. 66.67% of patients in the Solifenacin group and 44.45% in the tolterodine group had side effects.
Conclusion: Six out of 10 patients are likely to have bladder spasms post-prostatectomy. Although both Solifenacin and tolterodine are efficacious in relieving symptoms, Solifenacin is superior and associated with more side effects.
Electrographic significance of Periodic Discharges and association with etiology and outcome in tertiary care hospital, a retrospective cohort study
Authors: Imtiaz Hina , Memon Zainab Aslam Saeed , Khan Ayisha Farooq , Kanwar Dureshahwar , Awan Safia
Published: October 2024

Background: Periodic discharges in electroencephalograms (EEGs) represent rhythmic wave patterns and can indicate acute or subacute brain damage. Although they may predispose patients to seizures, not all are epileptiforms. This study focused on electrographical periodic discharges and aimed to elucidate their frequency, etiological associations, and clinical outcomes within a tertiary care hospital setting.
Results: This retrospective observational cohort study spanned two years, from January 2021 to January 2023. It included patients aged 18 years and above with EEG-confirmed periodic discharges. Data, including demographics, symptoms, EEG findings, neuroimaging results, treatment, and outcomes, were collected and analyzed using SPSS version 22.
Of the 41 patients analyzed, 51.2% were female, with an average age of approximately 58.5 years. Generalized tonic-clonic seizures were the most common clinical presentation (48.8%), with ischemic stroke as the leading etiological factor (31.7%). Lateralized periodic discharges (LPDs) were the most common EEG finding. Notably, 34% of patients exhibited chronic imaging changes, primarily encephalomalacia and gliosis. The majority (87.8%) were discharged home, with a minority (12.2%) experiencing mortality, often associated with status epilepticus or metabolic encephalopathy.
Conclusion: This study highlights the importance of recognizing periodic discharges in EEGs within the context of a tertiary care hospital. The findings of this study emphasize the potential gravity of periodic discharges, as indicated by mortality rates and functional outcomes. An improved understanding of these periodic discharges and their associated conditions can guide clinical decision-making and enhance patient care within tertiary care hospital settings.
Dual-fluorescence labeling of pseudorabies virus for live-cell tracking virus entry and replication
Authors: Wu Hongxia , Li Mingzhi , Pan Li , Xiang Guangtao , Li Lian-Feng , Wang Tao , Luo Rui , Li Yongfeng , Liu Di , Zhai Huanjie , Assad Moon , Song Xin , Wang Yanjin , Gallardo Franck , Sun Yuan , Qiu Huaji
Published: October 2024

Pseudorabies virus (PRV) is a neurotropic herpesvirus. It is not easy to tracking the whole replication progess of PRV, especially the nascent viral genome in the host cells. In this study, we developed a dual-fluorescence-labeled PRV (rPRV-Anchor3-mCherry) with the viral genome and the envelope protein gM labeled by Anchor DNA labeling system and mCherry, respectively. Through single-virus tracking of rPRV-Anchor3-mCherry, we observed that PRV invaded mouse neuroblastoma Neuro2a (N2a) cells via both endocytosis and plasma membrane fusion pathway. During the replication stage, parental and progeny viral genome of rPRV-Anchor3-mCherry in the cell nuclei could be visible, and viral nucleocapsid appeared more specifically than traditional capsid protein labeled PRV particles (rPRV-VP26-EGFP). We found that numerous progeny viral particles were produced in the nucleus, causing the nucleus membrane to break using three-dimensional (3D) live-cell imaging and electron microscopy. Moreover, Our findings confirmed that simultaneously targeting of the UL9 and UL54 genes using a CRISPR-Cas9 system led to the complete inhibit PRV replication. rPRV-Anchor3-mCherry can be used to research multiple steps of the viral cycle.
A Case of Lacrimal Gland Ductal Carcinoma: Clinical, Morphological and Genetic Characterization
Authors: Jin Yanlin , Wu Qinbo , Qian Lili , Ye Meihua , He Xianglei
Published: October 2024

Lacrimal gland ductal carcinoma is a rare, highly invasive tumor associated with a poor prognosis, arising from the lacrimal gland ductal epithelium. This study presents a rare case of lacrimal gland ductal carcinoma, analyzed through histopathology, immunohistochemistry (IHC) staining, fluorescence in situ hybridization (FISH), and whole-exome sequencing (WES) following surgical excision. Pathological examination confirmed a lacrimal gland ductal carcinoma with different structure features, including a solid pattern with comedo necrosis, cribriform pattern, and trabecular pattern. IHC assays demonstrated negative expression for P63, Calponin, CK5/6, SMA, S100, CK14, CD117, and GCDFP-15 in the tumor cells, while CK (Pan), EMA, and mammaglobin were positively expressed. Additionally, AR, GATA3, and HER-2 showed focal weak positivity. FISH analysis revealed a positive PLAG1 rearrangement and a negative HMAG1 rearrangement. WES revealed mutations in BAX, RB1, USP48, SDHB, COL17A1, COL6A6, PIK3CG, PIK3C2B, POLE, and APOBEC3G, suggesting these as potential driver genes in lacrimal gland ductal carcinoma. The patient remained alive at the time of this report.
Motor Skills and Neurological Soft Signs: Are They Only Clinical Differences or Reflection of Distinct Etiopathogenesis in Tic Disorder and Primary Stereotypic Movement Disorder?
Authors: Aliyev Ecem Selin Akbas , Ünal Dilek
Published: October 2024

While Tic Disorders (TD) and Stereotypic Movement Disorder (SMD) are commonly comorbid in pediatric clinics, their clinical and etiological differences remain poorly understood. We aimed to investigate the clinical features that differentiate between TD and primary SMD by evaluating neurological soft signs (NSS) and motor skills. The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 (K-SADS-PL) and Sociodemographic and Clinical Data Form were administered to the children and their parents. The clinician completed the Yale Global Tic Severity Scale (YGTSS), Repetitive Behavior Scale-Revised (RBS-R) and Neurological Evaluation Scale (NES). The Nine-Hole Peg Test was used for fine motor skills, the 1-Minute Sit-to-Stand Test for gross motor skills, the Flamingo Balance Test for static balance, and the Finger-to-Nose Test for bilateral coordination. Parents completed the Conners Parent Rating Scale-Revised Short Form (CPRS-RSF) and the Developmental Coordination Disorder Questionnaire-Revised (DCDQ-R). Our sample consisted of 20 TD, 20 primary SMD, 13 ADHD patients, and 20 healthy controls (HCs). Sequencing of the complex motor acts scores of NES were significantly higher in the SMD group than in HCs. The primary SMD group demonstrated significantly lower dominant hand performance on the Nine-Hole Peg Test than the TD group. Children with primary SMD had significantly lower scores of 1-minute sit-to-stand test; higher total and subscale scores of DCDQ-R and higher developmental coordination disorder risk than HCs. Our findings offer valuable insights into the distinct etiopathogenesis of TD and primary SMD, providing a foundation for future neurobiological research.
Contribution of ASE in the MOPA system output signal
Authors: Trigub Maxim V. , Vasnev Nikolai A.
Published: October 2024

The paper is devoted to research the contribution of ASE in the MOPA system output signal and time dependence of the signal-to-noise ratio. The results demonstrate how the output signal depends on time delay between ASE of power amplifier and laser radiation of master oscillator. The time delay (td) varied over the wide range (‒36; +24) ns, where «+» sign that the input signal enters the quantum amplifier (power amplifier) before the formation of its ASE. The light waveforms (ASE, input signal, output signal) and power dependencies are presented. The contribution of ASE in each case is determined. The results allow to estimate the signal-to-noise ratio. The maximal value of the output radiation power was 3,87 W at time delay td = + 4.7 ns, when the first maximum of input signal is approximately consistent with the ASE front.