bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and predictive value of mismatch repair deficiency in gastric and gastroesophageal junction adenocarcinoma patients receiving neoadjuvant or adjuvant chemotherapy
Authors: Li Ziyu , Wang Yinkui , Ying Xiangji , Zhang Li , Gao Xiangyu , Jia Yongning , Zhang Lianhai , Wu Aiwen , Su Xiangqian , Ji Jiafu
Published: September 2021

Background and objectives

Evidence is inconclusive regarding the prognostic significance of deficient DNA mismatch repair (dMMR) in gastric and gastroesophageal junction (GEJ) adenocarcinoma patients receiving chemotherapy. We aim to explore such associations with a large cohort.

Methods

We retrospectively identified a consecutive cohort of patients who had histology proven gastric or GEJ adenocarcinoma and received neoadjuvant chemotherapy plus surgery or upfront surgery plus adjuvant chemotherapy. MMR status was assessed by immunohistochemistry staining on surgical specimen. The association of MMR status with tumor regression grade (TRG), overall survival (OS), and disease‐free survival (DFS) were analyzed.

Results

In total, 1568 patients received neoadjuvant or adjuvant chemotherapy, of which 128 (8.2%) had dMMR tumors. No significant difference was found in the frequencies of TRG categories between proficient MMR (pMMR) and dMMR tumors (p = .62). Among patients receiving neoadjuvant chemotherapy, dMMR status was associated with better OS (log‐rank p = .044) and DFS (log‐rank p = .022) in the univariate analysis; this association became nonsignificant after adjusting for pathologic stages and other prognostic factors. Similar results were found for patients receiving adjuvant chemotherapy.

Conclusions

dMMR status was not significantly associated with OS and DFS among gastric and GEJ adenocarcinoma patients with neoadjuvant and adjuvant platinum and fluorouracil‐based chemotherapy.
The Visualized Urethral Mobility Profile in Stress Urinary Incontinence Described by Four‐Dimensional Transperineal Ultrasound
Authors: Zhao Baihua , Wen Lieming , Liu Dan , Huang Shanya
Published: September 2021

Objectives

To describe the urethral mobility during urine leaking in stress urinary incontinence (SUI) by transperineal ultrasound (TPUS) with urethral mobility profile (UMP) analysis.

Methods

This was a prospective study of 380 women who had a cough stress test (CST) with TPUS. UMP software automatically placed six equidistant points from the bladder neck (Point 1) to the external urethral meatus (Point 6) and determined their x and y coordinates relative to the symphysis pubis. Urethral mobility vector of Points 1–6 (Vectors 1–6) and the distance between the six points and the symphysis (Dist. 1–6) were calculated and compared between the two groups. The visualized UMP was created by reproducing the positions of the six points at rest and on Valsalva.

Results

Valid data of 188 women with SUI and 174 continent women were analyzed. The mean age of all 362 women was 49.3 years. Mean body mass index in the SUI group was significantly increased (23.8 vs 22.2 kg/m2, P < .001). During CST, Vectors 1–6 and Dist. 2–6 were significantly increased (all P < .005) in the SUI group. The UMP showed the mid‐urethral rotated down around the symphysis pubis. The upper urethral profile in the two groups was similar. But the gap between the mid‐urethra and the symphysis was wider in the SUI group.

Conclusions

The visualized UMP illustrated the mid‐urethral hypermobility in SUI by showing a wider gap due to the unstable connection between the mid‐urethra and the symphysis pubis.
Impact of the COVID‐19 Pandemic on the 2021 Otolaryngology Residency Match: Analysis of the Texas STAR Database
Authors: Lenze Nicholas R. , Mihalic Angela P. , Kovatch Kevin J. , Thorne Marc C. , Kupfer Robbi A.
Published: September 2021

Objectives/Hypothesis

To estimate the impact of the coronavirus disease 2019 (COVID‐19) pandemic on the 2021 otolaryngology match with regard to geographic clustering, interview distribution, applicant‐reported costs, and matched applicant characteristics.

Study Design

Retrospective cohort study.

Methods

Survey data from applicants to otolaryngology residency programs were obtained from the Texas Seeking Transparency in Applications to Residency database. Applicant differences between the 2021 match year and prior match years (2018, 2019, and 2020) were analyzed using two‐sided t‐tests, Chi‐square tests, and Fisher's exact tests.

Results

A total of 442 otolaryngology residency applicants responded to the survey, including 329 from the match years 2018 to 2020 and 113 from match year 2021. In 2021, 30.7% of responding applicants reported matching at a program where they had a geographic connection, compared to 40.0% in prior years (P = .139). Matched applicants in 2021 reported attending less interviews than applicants in prior years (mean 12.2 vs. 13.3, P = .040), and 26.1% of responding applicants reported matching at a program where they sent a preference signal. Applicants in the 2021 match reported significantly lower total costs than applicants in prior years (mean difference −$5,496, 95% confidence interval −$6,234 to −$4,759; P < .001). Compared to prior match years, matched applicants in 2021 had no meaningful differences in characteristics such as United States Medical Licensing Exam board scores, clerkship grades, honors society memberships, research output, volunteer experiences, or leadership experiences.

Conclusion

Based on this sample, there was no evidence of significant interview hoarding or increased geographic clustering in the 2021 otolaryngology match, and the COVID‐19 pandemic did not appear to result in significantly different matched applicant characteristics.

Level of Evidence

4 Laryngoscope, 132:1177–1183, 2022
CO‐CREATION LEADERSHIP
Authors: Jackson Terry
Published: September 2021

The author discusses co‐creation leadership; describing Co‐creation as “the collaboration among interested parties to create something better than either could have created on its own.” In today's increasingly complex world, where problems reach global levels of concern, “solving for the needs of one stakeholder must take into account the needs of all stakeholders, lest creating solutions that solve one problem only contribute to creating another.” It ends with what he calls a “Recipe,” in his words: R‐Revolutionary Results E‐Execution C‐Culture I‐Intention P‐Purpose E‐Evolution. There are many practical benefits, including that “when all people are more educated and prosperous, society as a whole becomes more educated and prosperous.” Business examples are drawn from companies like the Lego Corporation and the South Korean cosmetics retailer Missha. In Public health he discusses the unprecedented cooperation leading to COVID‐19 vaccines. In society and government, he uses historic examples from the United States Senate; and the International Space Station (ISS0, within Science. In how to co‐create, he notes that “organizations that do not value their employees’ contributions will lose the best of them to those that do. Those who remain will become more disengaged, and more problematic.”
Encoding true second‐order arithmetic in the real‐algebraic structure of models of intuitionistic elementary analysis
Authors: Erdélyi‐Szabó Miklós
Published: September 2021

Based on the paper [4] we show that true second‐order arithmetic is interpretable over the real‐algebraic structure of models of intuitionistic analysis built upon a certain class of complete Heyting algebras.
Flexible and Highly Conductive AgNWs/PEDOT:PSS Functionalized Aramid Nonwoven Fabric for High‐Performance Electromagnetic Interference Shielding and Joule Heating
Authors: Li Lele , Sun Baojie , Li Wenyue , Jiang Liang , Zhou Yanfen , Ma Jianwei , Chen Shaojuan , Ning Xin , Zhou Feng‐Lei
Published: September 2021

High‐performance multifunctional textiles are highly demanded for human health‐related applications. In this work, a highly conductive nonwoven fabric is fabricated by coating silver nanowires (AgNWs)/poly(3,4‐ethyl enedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) on a poly(m‐phenylene isophthalamide) (PMIA) nonwoven fabric through a multistep dip coating process. The as‐prepared PMIA/AgNWs/PEDOT:PSS composite nonwoven fabric shows an electrical resistance as low as 0.92 ± 0.06 Ω sq−1 with good flexibility. The incorporation of the PEDOT:PSS coating layer improves the adhesion between AgNWs and PMIA nonwoven fabric, and also enhances the thermal stability of the composite nonwoven fabric. Electromagnetic interference (EMI) shielding and Joule heating performances of the PMIA/AgNWs/PEDOT:PSS composite nonwoven fabric are also investigated. The results show that the average EMI shielding effectiveness (SE) of the single‐layer nonwoven fabric in X‐band is as high as 56.6 dB and retains a satisfactory level of SE after being washed, bended, and treated with acid/alkali solution and various organic solvents. The composite nonwoven fabric also exhibits low voltage‐driven Joule heating performance with reliable heating stability and repeatability. It can be envisaged that the multifunctional PMIA/AgNWs/PEDOT:PSS nonwoven fabric with reliable stability and chemical robustness can be used in EMI shielding devices and personal thermal management products.
Deep analysis of the LRTOMTc.242G>A variant in non‐syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies
Authors: Mosrati Mohamed Ali , Fadhlaoui‐Zid Karima , Benammar‐Elgaaied Amel , Gibriel Abdullah Ahmed , Ben Said Mariem , Masmoudi Saber
Published: September 2021

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogenic and is associated with NSHL in both humans and mice. The aim of this study is to determine the carrier frequency for the LRTOMT c.242G>A variant and also to estimate its age in addition to evaluating its diagnostic potential as a deafness biomarker among various populations and ethnicities in Northern African countries. A total of 179 Tunisian and 34 Libyan unrelated deafness patients were screened for this variant. The homozygous c.242G>A variant was found in 5.02% and 2.94% in Tunisian and Libyan families, respectively. Subsequent screening for this variant in 263 healthy controls of various ethnicities (136 Tunisian Berbers, 32 Andalusian and 95 Tunisian from undefined ethnic origin) revealed higher frequency for the heterozygous state among Tunisians of Berber origin only (19.11%). Genotyping 7 microsatellite markers nearby the variant location in ARNSHL patients who had the homozygous variant revealed the same haplotype suggesting a common founder origin for this variant. The age of this variant was estimated to be between 2025 and 3425 years (this corresponds to 3400 years when the variant rate was set at 10−3 or 2600 years when the variant rate is set at 10−2), spreading along with the Berber population who migrated to North Africa. In conclusion, the LRTOMT c.242G>A homozygous variant could be used as a useful deafness biomarker for North African ARNSHL patients meanwhile the heterozygous variant could be utilized in genealogical studies for tracing those of the Berber ethnic group.
Ulam's type stabilities for conformable fractional differential equations with delay
Authors: Wang Sen , Jiang Wei , Sheng Jiale , Li Rui
Published: September 2021

In this paper, we investigate the existence and uniqueness of solutions and Ulam's type stabilities including the well‐known Ulam–Hyers stability and the newly extended Ulam–Hyers conformable exponential stability for two classes of fractional differential equations with the conformable fractional derivative and the time delay. The Banach contraction principle, the technique of Picard operator, the Grönwall integral inequalities, and generalized iterated integral inequality in the sense of conformable fractional integral are the main tools for deriving our main results. Finally, several illustrative examples will be presented to demonstrate our work.
The changing pattern of acute spinal referrals during primary and secondary waves of the COVID‐19 pandemic
Authors: Naskar Rajib , Baryeh Kwaku W. , Pavuluri Sindhu , Rajagopal Trichy
Published: September 2021

Introduction

The COVID‐19 pandemic has had a devastating effect on health systems globally. This led to changes in patient access to healthcare particularly spinal services. This study investigates the impact of the pandemic on the volume of patients being referred to and accessing spinal services during both the first and second waves.

Methods

All emergency spinal referrals and related hospital attendances to the emergency department in a busy district general hospital were analysed. The data were evaluated at three time points each covering a 3‐month period. Data collected included patient demographics, duration and nature of symptoms, reason for referral, clinical and MRI findings, length of stay in hospital, any interventions performed and the follow‐up plan.

Results

There were a total of 316 emergency referrals across the three time periods. The number of referrals fell by 15% between the pre‐COVID‐19 period and the first wave. Comparing the first and second waves, the number of referrals was increased by 58%. Comparing the second wave to the pre‐COVID‐19 period, referrals were 34% greater in the second wave (p < 0.005).

Conclusion

We highlight an increase in referrals to our spinal service during the secondary wave, having fallen during the first wave. We hypothesise that the increase in referrals, despite similar restrictions to the first wave, is a result of changing patterns of behaviour due to the fear of contracting COVID during the first wave and difficulty in accessing primary care services in the second wave.
Neurological safety and efficacy of darifenacin and mirabegron for the treatment of overactive bladder in patients with history of cerebrovascular accident: A prospective study
Authors: Vasudeva Pawan , Kumar Amitabh , Yadav Siddharth , Kumar Niraj , Chaudhry Neera , Prasad Vishnu , Nagendra Rao Swatantra , Yadav Prashant , Patel Samarth
Published: September 2021

Objectives

To evaluate the neurological safety and clinical efficacy of darifenacin and mirabegron in patients with a history of cerebrovascular accident (CVA) who had overactive bladder (OAB) symptoms.

Methods

This prospective randomized study, approved by the institute's ethics committee, was carried out at a tertiary care center from December 2018 to June 2020. Treatment naïve adult patients with a past history of CVA with stable neurological status for atleast past 3 months with symptoms of OAB for 3 or more months were included. Eligible patients received either darifenacin or mirabegron for a period of 3 months and various parameters on the 3‐day International Consultation on Incontinence Questionnaire (ICIQ) bladder diary, the Montreal Cognitive Assessment—Basic score (MoCA‐B), and the adverse events at 3 months posttreatment were compared to that at the baseline.

Results

A total of 60 patients were included, 30 in each arm. After 3 months of treatment with darifenacin or mirabegron, the majority of the ICIQ bladder diary parameters improved and there was no deterioration in the cognitive function as noted on the MoCA‐B score in either of the arms. On intergroup comparison, the mean change in bladder diary parameters and the MoCA‐B scores was similar between the two groups.

Conclusion

Darifenacin and mirabegron, in the short term, do not adversely affect the cognitive function in patients with a history of CVA with OAB symptoms. Both are safe and effective treatment options in patients with OAB post‐CVA.
Patient-Reported Outcomes with Selpercatinib Treatment Among Patients with RET-Mutant Medullary Thyroid Cancer in the Phase I/II LIBRETTO-001 Trial
Authors: Wirth Lori J , Robinson Bruce , Boni Valentina , Tan Daniel S W , McCoach Caroline , Massarelli Erminia , Hess Lisa M , Jen Min-Hua , Kherani Jennifer , Olek Elizabeth , Subbiah Vivek
Published: September 2021

Background

Medullary thyroid cancer (MTC) standard of care includes multikinase inhibitors (MKIs), which can exacerbate disease-related diarrhea, primarily because of non-RET kinase inhibition. We report diarrhea and other patient-reported outcomes (PROs) with selpercatinib, a highly selective RET inhibitor, among patients with RET-mutant MTC in the ongoing, phase I/II LIBRETTO-001 trial.

Materials and Methods

Instrument completion time points were baseline (cycle 1, day 1) and approximately every other 28-day cycle until cycle 13 (every 12 weeks thereafter) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and baseline, weekly during cycle 1, and day 1 of every cycle for the modified Systemic Therapy–Induced Diarrhea Assessment Tool (mSTIDAT). A ≥10-point change from baseline in domain score was considered clinically meaningful. PROs were summarized through cycle 13 in all patients and by subgroups with or without prior exposure to MKIs vandetanib and/or cabozantinib (V/C).

Results

Among the overall MTC population (n = 226), 88 (39%) and 124 (55%) patients comprised the V/C-naïve and previous V/C subgroups, respectively. Compliance was >85% for both instruments at each time point. Most patients maintained/improved in all health-related quality of life (HRQoL) subscales throughout treatment. Improvements in diarrhea were clinically meaningful in 43.5% of patients overall and in 36.8% and 51.3% of V/C-naïve and previous V/C subgroups, respectively. At baseline, 80.4% of all patients reported diarrhea on mSTIDAT. The percentage of patients who reported diarrhea was reduced to less than half of all patients (range: 33.3%–48.3%) after cycle 2.

Conclusion

These interim results demonstrate that patients with RET-mutant MTC improved/remained stable on all domains of HRQoL during treatment with selpercatinib. Future analyses will be conducted as the data mature.
Assessment of PD-L1 Expression on Circulating Tumor Cells for Predicting Clinical Outcomes in Patients with Cancer Receiving PD-1/PD-L1 Blockade Therapies
Authors: Tan Zhaoli , Yue Chunyan , Ji Shoujian , Zhao Chuanhua , Jia Ru , Zhang Yun , Liu Rongrui , Li Da , Yu Qian , Li Ping , Hu Zhiyuan , Yang Yanlian , Xu Jianming
Published: September 2021

Background

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade immunotherapies have changed the landscape of cancer therapy. However, the main limitation of these therapies is the lack of definitively predictive biomarkers to predict treatment response. Whether PD-L1 expression on circulating tumor cells (CTCs) is associated with the clinical outcomes of immunotherapy remains to be extensively investigated.

Materials and Methods

One hundred fifty-five patients with different advanced cancers were enrolled in this study and treated with anti-PD-1/PD-L1 monoclonal antibodies. Using the Pep@MNPs method, CTCs were isolated and enumerated. The PD-L1 expression levels were analyzed by an immunofluorescence assay for semiquantitative assessment with four categories (negative, low, medium, and high).

Results

Prior to immunotherapy, 81.93% (127/155) of patients had PD-L1-positive CTCs, and 71.61% (111/155) had at least one PD-L1-high CTC. The group with PD-L1-positive CTCs had a higher disease control rate (DCR) (71.56%, 91/127), with a DCR of only 39.29% (11/28) for the remaining individuals (p = .001). The objective response rate and DCR in PD-L1-high patients were higher than those in the other patients (32.44% vs. 13.64%, p = .018 and 75.68% vs. 40.91%, p < .0001, respectively). The reduction in the counts and ratios of PD-L1-positive CTCs and PD-L1-high CTCs reflected a beneficial response to PD-1/PD-L1 inhibitors. Furthermore, patients with PD-L1-high CTCs had significantly longer progression-free survival (4.9 vs. 2.2 months, p < .0001) and overall survival (16.1 vs. 9.0 months, p = .0235) than those without PD-L1-high CTCs.

Conclusion

The PD-L1 level on CTCs may serve as a clinically actionable biomarker for immunotherapy, and its dynamic changes could predict the therapeutic response.

Implications for Practice

This study was designed to investigate the role of programmed death-ligand 1 (PD-L1) expression on circulating tumor cells in predicting and monitoring response to programmed death-1 (PD-1)/PD-L1 blockade immunotherapies in patients with advanced cancer. The results of the study showed that PD-L1-high-expression circulating tumor cells (CTCs) were both a predictive biomarker and a prognostic factor in patients with advanced cancer treated with anti-PD-1/PD-L1 monoclonal antibodies. These observations suggest that PD-L1 level on CTCs is a potential clinical biomarker for immunotherapy.
Self‐reported cognitive impairment in cervical cancer survivors: A cross‐sectional study
Authors: Areklett Elisabeth Wang , Fagereng Elisabeth , Bruheim Kjersti , Andersson Stein , Lindemann Kristina
Published: September 2021

Objective

Cancer‐related cognitive impairment (CRCI) is a major obstacle for cervical cancer survivors, preventing the return to their social life. This study assessed the prevalence of CRCI in cervical cancer survivors and studied the association of self‐reported cognitive impairment with treatment regimen and the quality of life (QoL) domains depression, anxiety, and fatigue.

Methods

Six hundred twenty one cervical cancer survivors, treated with combined chemo‐radiotherapy (CCRT) (n = 458) or surgery only (n = 163) were invited in this cross‐sectional study. Self‐reported cognitive function was assessed using the Functional Assessment of Cancer Therapy‐Cognitive Function (FACT‐Cog). Fatigue and psychological distress were assessed using EORTC‐QLQ C30 and Hospital Anxiety and Depression Scale (HADS).

Results

Data of 254 women (40.9%) was available for the analysis. Of those, 204 (80.3%) women had received CCRT and 50 (19.7%) surgery only. In the whole cohort, 42.5% reported significant cognitive impairment. In both treatment groups cognitive complaints were significantly associated with anxiety, depression, and fatigue (all p < 0.001). CCRT was strongly associated with increased risk of CRCI (OR = 4.02, 95% CI = 1.57–10.25). Anxiety, depression, and fatigue increased the risk of CRCI by 13% (OR: 1.13, 95% CI 1.03–1.23), 16% (OR 1.16, 95% CI 1.04–1.28) and 2% (OR 1.02, 95% CI 1.00–1.03), respectively.

Conclusion

Almost half of the cervical cancer survivors after CCRT report significant cognitive impairment. CRCI is associated with other indicators of poor QoL, such as depression, anxiety and fatigue. An increased understanding of the specific cognitive domains affected and of the associated late effects like fatigue is crucial to customize successful interventions.
Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial
Authors: Butel Thibault , Angoulvant François , Filipovic‐Pierucci Antoine , Milcent Karen , Teglas Jean‐Paul , Bellêttre Xavier , Claudet Isabelle , Gras‐le Guen Christèle , de Pontual Loïc , Minodier Philippe , Dubos François , Brouard Jacques , Soussan‐Banini Valérie , Degas‐Bussiere Vanessa , Gatin Amélie , Schweitzer Cyril , Epaud Ralph , Ryckewaert Amélie , Cros Pierrick , Marot Yves , Flahaut Philippe , Saunier Pascal , Babe Philippe , Patteau Géraldine , Delebarre Mathilde , Titomanlio Luigi , Vrignaud Bénédicte , Trieu Thanh‐Van , Tahir Abdelilah , Regnard Delphine , Micheau Pascale , Charara Oussama , Henry Simon , Ploin Dominique , Panjo Henri , Vabret Astrid , Bouyer Jean , Durand‐Zaleski Isabelle , Gajdos Vincent
Published: September 2021

Introduction

Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1‐month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED).

Methods

Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority.

Results

A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756–2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France.

Discussion

Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.
The Firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement
Authors: Takezawa Kentaro , Fujita Kazutoshi , Matsushita Makoto , Motooka Daisuke , Hatano Koji , Banno Eri , Shimizu Nobutaka , Takao Tetsuya , Takada Shingo , Okada Koichi , Fukuhara Shinichiro , Kiuchi Hiroshi , Uemura Hirotsugu , Nakamura Shota , Kojima Yoshiyuki , Nonomura Norio
Published: September 2021

Background

The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement.

Methods

We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate‐enlargement (PE) group; those with prostate volumes <30 ml were defined as the non‐PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups.

Results

The PE group included 66 patients; the non‐PE group included 62 patients. Age, body mass index, and prostate‐specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non‐PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non‐PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015).

Conclusion

The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.
Increased risk of postoperative in‐hospital complications after radical prostatectomy in patients with prior organ transplant
Authors: Wenzel Mike , Würnschimmel Christoph , Chierigo Francesco , Tian Zhe , Shariat Shahrokh F. , Terrone Carlo , Saad Fred , Tilki Derya , Graefen Markus , Banek Severiné , Kluth Luis A. , Mandel Philipp , Chun Felix K. H. , Karakiewicz Pierre I.
Published: September 2021

Background

To analyze postoperative, in‐hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP).

Methods

From National Inpatient Sample (NIS) database (2000–2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in‐hospital complications.

Results

Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in‐hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in‐hospital mortalities were recorded in transplant patients after RP.

Conclusions

Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in‐hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
The role of histopathological and biochemical parameters for predicting metastatic disease on 68Ga‐PSMA‐11 PET in prostate cancer
Authors: Aydos Uğuray , Çetin Serhat , Akdemir Ümit Özgür , Budak Fırat Çağlar , Ateş Seda Gülbahar , Koparal Murat Yavuz , Gönül İpek Işık , Gülbahar Özlem , Sözen Sinan , Atay Lütfiye Özlem
Published: September 2021

Background

The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on 68Ga‐PSMA PET images.

Methods

Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent 68Ga‐PSMA‐11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as “PET positive” and “PET negative” according to the presence of pathologic extraprostatic PSMA involvement. “PET positive” patients were additionally divided into two groups: oligometastatic (1‐3 metastatic lesion) and multimetastatic (>3 metastatic lesions).

Results

The mean age of patients was 66.8 ± 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in “PET positive” group compared to “PET negative” group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low‐intermediate risk groups (ISUP 1‐3 and total PSA ≤ 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high‐risk group (ISUP 4‐5 or total PSA > 20 ng/ml or PSAD ≥ 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05).

Conclusions

In this study, 68Ga‐PSMA‐11 PET positivity was significantly higher in the high‐risk patient group than in the low‐intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high‐risk patients.
Tissue cholesterol metabolism and prostate cancer aggressiveness: Ethno‐geographic variations
Authors: Lethongsavarn Vincent , Pinault Michèle , Diedhiou Abdoulaye , Guimaraes Cyrille , Guibon Roseline , Bruyère Franck , Mathieu Romain , Rioux‐Leclercq Nathalie , Multigner Luc , Brureau Laurent , Fournier Georges , Doucet Laurent , Blanchet P. , Fromont Gaëlle
Published: September 2021

Background

Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri‐prostatic adipose tissue (PPAT) has been shown to differ according to the ethno‐geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African‐Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues.

Methods

The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African‐Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3–5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays.

Results

The amount of cholesterol esters was lower in PPAT from African‐Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African‐Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP‐2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP‐2 expression was strongly associated with that of Zeb1, a key player in the epithelial‐to‐mesenchymal transition (EMT) process.

Conclusion

These results suggest that cholesterol metabolism differs according to the ethno‐geographic origin, in both PPAT and cancer tissues. In African‐Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population.
Cost‐conscious robotic restorative proctectomy has similar economic and oncologic outcomes to open restorative proctectomy: Results of a long‐term follow‐up study
Authors: Cengiz Turgut Bora , Benlice Cigdem , Ozgur Ilker , Kaya Gizem , Aytac Erman , Kalady Matthew F. , Steele Scott R. , Liska David , Gorgun Emre
Published: September 2021

Background

In this study, we hypothesised that the direct hospital costs of robotic restorative proctectomy (RP) would be similar to those of open RP when a cost‐conscious approach was employed in rectal cancer patients.

Methods

We included consecutive patients with rectal cancer who underwent RP between 12/2011 and 10/2014. A cost‐conscious approach was employed in robotic surgery. We compared demographics, long‐term oncologic outcomes, and direct hospital costs between the open and robotic groups.

Results

There were 32 robotic and 68 open RP procedures performed. Compared to open RP, the robotic RP group had a longer operative time but less estimated blood loss, intraoperative transfusions, overall short‐term morbidity, decreased length of stay. After the initial five robotic cases, overall hospital costs were comparable between the groups (1 ± 0.5 vs. 1 ± 0.4, open and robotic RP, respectively, p = 0.90).

Conclusion

Increasing surgeon experience and a cost‐conscious approach may improve the value of care of robotic RP in patients with rectal cancer.
The impact of social distancing on community case count in the United States: Testing the efficacy of protection motivation theory during early stages of the COVID‐19 pandemic
Authors: Yeom Minkyu , Stewart Fran , Stewart Alice
Published: September 2021

Centuries of practice and an array of public health literature support social distancing (SD), or self‐quarantine, as a valuable nonpharmaceutical intervention. To convince individuals to engage in behaviors that limit infection, public health professionals communicate risk and hazard based on application of protection motivation theory (PMT). The COVID‐19 pandemic presents an opportunity to explore the efficacy of PMT in the context of a novel coronavirus with unique public health implications. We test an integrative conceptual model of social distancing compliance in U.S. counties and examine the mediating impact of SD on community spread of infection. We find that PMT does impact individual behavior, observing that the proportion of vulnerable populations affects social distancing compliance. However, actions to protect individual health are made within the context of economic concerns and priorities. While results indicate that PMT influences behavior, the expected relationship between that behavior and spread of disease in the community is not found. We do not repudiate SD or the value of PMT, but we suggest that these results may indicate that communication of risk in the context of COVID‐19 may need community, as well as individual, framing.
A Ratiometric pH Responsive Fluorescence Probe for Monitoring Wide pH Range
Authors: Sahana Sunanda , Sharma Vivekanand , Bharadwaj Parimal K.
Published: September 2021

A novel ratiometric pH probe has been designed and synthesized on a Rhodamine B platform bearing one anthraquinone moiety and the photochemical properties of this system are evaluated. Changing the pH from acidic to basic condition, this probe exhibited 92 nm red‐shift of the emission maximum. This change is sufficiently large to permit its use as a ratiometric pH probe. With fast response time this chemosensor is fully reversible which is important and advantageous for practical applications. Furthermore, the pKa values of this probe can be predicted from the fluorescence titration. This design strategy is very simple and being modular, can be applicable to develop ratiometric pH probes for various applications.
Allometric Regression of Snake Body Length from Head Image Measurements
Authors: SIERS SHANE R.
Published: September 2021

As in many fields of wildlife research and management, camera devices and photogrammetry have become an integral part of the toolkit for exploring otherwise‐unseen aspects of the biology, behavior, and control of the invasive brown treesnake (Boiga irregularis) on Guam. Because brown treesnakes are cryptic and nocturnal, and nearly all aspects of their ecology are influenced by snake size, methods are needed to estimate snake size from images captured by infrared wildlife cameras. Unfortunately, it is difficult to capture images of an entire snake's length at a controlled distance from a simple camera setup. Here, I describe the allometric relationships between brown treesnake body length and potential predictors: head measurements, sex, and body condition. Head length (HL) was the most important predictor of body length, alone accounting for 95.9% of the variation in brown treesnake snout‐vent length (SVL). We provide simple regression equations for predicting brown treesnake length from head measurements, an example of how to extract measurements from images, and a convenient lookup table for predicting SVL and 80% prediction intervals from HL alone. Coupled with a simple camera setup that controls subject distance and includes size standards in the image, we can estimate brown treesnake body size from images that include only the head when photographed from above. These methods have been developed to enable ongoing assessments of brown treesnake predation risk following landscape‐scale suppression efforts that could enable the reintroduction of extirpated native wildlife. Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Wildlife Society Bulletin published by Wiley Periodicals LLC on behalf of The Wildlife Society.
Novel drawing system approach to manufacture performant commercially pure aluminium fine wires
Authors: Caruso Serafino , Ambrogio Giuseppina
Published: September 2021

Due to its electro-mechanical properties, commercially pure aluminium wires have attracted the interest of automotive industry representing a functional and efficient economic solution to reduce vehicle’s weight leading to the diminishing of energy consumption and emissions in today’s society. However, to consolidate its use in this sector and in new market realities, it is necessary to increase the flexibility of the aluminium conductor wires, consenting their installation in very small spaces and with high curvatures, avoiding any failure and electrical conductivity decrease. Thus, the evolution of microstructure and service performance needs to be investigated and controlled to improve the service safety. The present research shows a new approach to continuously manufacture efficient long wires with smaller diameters and fine grains at room temperature. It is studied the strengthening effects (yield and tensile strength, plasticity, hardness), the electrical conductivity, and the microstructural changes of commercial 1370 pure aluminium (99.7% Al) when traditional wire drawing process is combined with equal channel angular drawing (ECAD) technique. The results of this proposed procedure of deformation “drawing-ECAD-drawing” show an evident benefit, compared to the classic technology of production of aluminium wire, obtaining fine grain structure product with superior mechanical strength and not influenced electrical conductivity. The proposed manufacturing approach leads to fine wires enhancing the material mechanical properties by microstructural evolution (i.e. grain size reduction) avoiding the traditional post manufacturing thermal treatments requiring a high amount of energy and time and careful steps.
Safety pharmacology of acute LSD administration in healthy subjects
Authors: Holze Friederike , Caluori Toya V. , Vizeli Patrick , Liechti Matthias E.
Published: September 2021

Rationale

Lysergic acid diethylamide (LSD) is used in psychiatric and psychological research and investigated as a potential treatment for medical and psychiatric disorders, including depression, anxiety, and cluster headache.

Objectives

Safety data on clinical safety are available from small studies but not from larger samples. We report safety pharmacology data from a large pooled study sample on acute effects of LSD in healthy subjects.

Methods

We conducted a pooled analysis of four double-blind, randomized, placebo-controlled, crossover studies that included a total of 83 healthy subjects and 131 single-dose administrations of LSD. LSD administrations were matched to dose groups according to measured LSD peak plasma concentrations to adjust for uncertainties in the correct LSD dose in some studies. Single doses were 25, 50, 100, and 200 µg of LSD base. We investigated subjective effects (self-rated any drug effect, good drug effect, bad drug effect, and anxiety), blood pressure, heart rate, body temperature, duration of the acute LSD response, acute (12 h) and subacute (24 h) adverse effects, reports of flashbacks, and liver and kidney function before and after the studies.

Results

LSD dose-dependently increased subjective, physiologic, and adverse effects. The dose–response curves for the proportions of subjects with a certain amount of a subjective effect were steeper and reached a higher maximum for positive acute subjective effects compared with negative acute subjective effects. Maximal ratings of > 50% good drug effects were reached in 37%, 91%, 96%, and 91% of the LSD administrations at 25, 50, 100, and 200 µg. Maximal ratings of > 50% bad drug effects were reached in 0%, 9%, 27%, 31% at 25, 50, 100, and 200 µg, respectively. Mean ratings of Oceanic Boundlessness were 10%, 25%, 41%, and 44%, and mean ratings of Anxious Ego-Dissolution were 3.4%, 13%, 20%, and 22% at 25, 50, 100, and 200 µg, respectively. The physiologic effects of LSD were moderate. None of the subjects had systolic blood pressure > 180 mmHg at any time. Peak heart rate > 100 beats/min was observed in 0%, 6%, 20%, and 25% of the subjects at 25, 50, 100, and 200 µg, respectively. Maximal heart rates of 129 and 121 beats/min were observed in one subject at the 50 and 200 µg doses, respectively. Peak body temperature > 38° was observed in 0%, 11%, 7%, and 34% at 25, 50, 100, and 200 µg, respectively. Mean acute adverse effect scores on the List of Complaints were 5.6, 9.2, 12, and 13 at 25, 50, 100, and 200 µg, respectively. Kidney and liver function parameters were unaltered. Six subjects reported transient flashback phenomena.

Conclusions

The single-dose administration of LSD is safe in regard to acute psychological and physical harm in healthy subjects in a controlled research setting.
Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking
Authors: Basińska-Szafrańska Anna
Published: September 2021

Objective

Rapid relapses after successful withdrawal occur even in apparently motivated benzodiazepine (BZD)-dependent patients. Regardless of known personality or biological (re-adaptation) issues, the aim of this open-label, single-arm, seminaturalistic study was to search for any detoxification errors contributing to failures.

Methods

The data came from 350 inpatients. Based on serum-BZD evolution criteria, the procedure was divided into four stages: substitution, accumulation, elimination and post-elimination observation. After switching the patients to a long-acting substitute (diazepam), to prevent data falsification due to unwanted overaccumulation, the doses were expeditiously reduced under laboratory feedback until accumulation stopped. With the start of effective elimination, the tapering rate slowed and was individually adjusted to the patient’s current clinical state. The tracking of both serum-BZD concentration and the corresponding intensity of withdrawal symptoms was continued throughout the entire elimination phase, also following successful drug withdrawal. Detoxification was concluded only after the patient's post-elimination stabilization.

Results

Regardless of various initial serum-BZD concentration levels and the customized dose-reduction rate, and despite the novel lab-driven actions preventing initial overaccumulation, elimination was systematically proven to be protracted and varied within the 2- to 95-day range after the final dose. Within this period, withdrawal syndrome culminated several times, with varying combinations of symptoms. The last crisis occurrence (typically 2–3 weeks after withdrawal) correlated with the final serum-BZD elimination. The factors that prolonged elimination and delayed the final crisis were patient age, duration of addiction, adjunct valproate medication and elimination stage start parameters growing with former overaccumulation.

Conclusions

The low-concentration detoxification stage is critical for patients’ confrontations with recurring withdrawal symptoms. Underestimated elimination time following drug withdrawal and premature conclusions of detoxification expose patients to unassisted withdrawal crises. Concentration tracking defines proper limits for medical assistance, preventing early relapses.
Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review
Authors: Aramburu Jorge , Antón Raúl , Rodríguez-Fraile Macarena , Sangro Bruno , Bilbao José Ignacio
Published: September 2021

Yttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade, computer simulations of hepatic artery hemodynamics during RE have been performed with the aim of better understanding and improving the therapy. In this review, we introduce the concept of computational fluid dynamics (CFD) modeling with a clinical perspective and we review the CFD models used to study RE from the fluid mechanics point of view. Finally, we show what CFD simulations have taught us about the hemodynamics during RE, the current capabilities of CFD simulations of RE, and we suggest some future perspectives.