bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between a J-domain co-chaperone and a specific Argonaute protein contributes to microRNA function in animals
Authors: Frédérick Pierre-Marc , Jannot Guillaume , Banville Isabelle , Simard Martin J
Published: April 2024

MicroRNAs (miRNAs) are essential regulators of several biological processes. They are loaded onto Argonaute (AGO) proteins to achieve their repressive function, forming the microRNA-Induced Silencing Complex known as miRISC. While several AGO proteins are expressed in plants and animals, it is still unclear why specific AGOs are strictly binding miRNAs. Here, we identified the co-chaperone DNJ-12 as a new interactor of ALG-1, one of the two major miRNA-specific AGOs in Caenorhabditis elegans. DNJ-12 does not interact with ALG-2, the other major miRNA-specific AGO, and PRG-1 and RDE-1, two AGOs involved in other small RNA pathways, making it a specific actor in ALG-1-dependent miRNA-mediated gene silencing. The loss of DNJ-12 causes developmental defects associated with defective miRNA function. Using the Auxin Inducible Degron system, a powerful tool to acutely degrade proteins in specific tissues, we show that DNJ-12 depletion hampers ALG-1 interaction with HSP70, a chaperone required for miRISC loading in vitro. Moreover, DNJ-12 depletion leads to the decrease of several miRNAs and prevents their loading onto ALG-1. This study uncovers the importance of a co-chaperone for the miRNA function in vivo and provides insights to explain how different small RNAs associate with specific AGO in animals.
CRISPR-Cas tools for simultaneous transcription & translation control in bacteria
Authors: Cardiff Ryan A L , Faulkner Ian D , Beall Juliana G , Carothers James M , Zalatan Jesse G
Published: April 2024

Robust control over gene translation at arbitrary mRNA targets is an outstanding challenge in microbial synthetic biology. The development of tools that can regulate translation will greatly expand our ability to precisely control genes across the genome. In Escherichia coli, most genes are contained in multi-gene operons, which are subject to polar effects where targeting one gene for repression leads to silencing of other genes in the same operon. These effects pose a challenge for independently regulating individual genes in multi-gene operons. Here, we use CRISPR-dCas13 to address this challenge. We find dCas13-mediated repression exhibits up to 6-fold lower polar effects compared to dCas9. We then show that we can selectively activate single genes in a synthetic multi-gene operon by coupling dCas9 transcriptional activation of an operon with dCas13 translational repression of individual genes within the operon. We also show that dCas13 and dCas9 can be multiplexed for improved biosynthesis of a medically-relevant human milk oligosaccharide. Taken together, our findings suggest that combining transcriptional and translational control can access effects that are difficult to achieve with either mode independently. These combined tools for gene regulation will expand our abilities to precisely engineer bacteria for biotechnology and perform systematic genetic screens.
Stereo-EEG features of temporal and frontal lobe seizures with loss of consciousness
Authors: Campora Nuria , Princich Juan Pablo , Nasimbera Alejandro , Cordisco Santiago , Villanueva Manuela , Oddo Silvia , Giagante Brenda , Kochen Silvia
Published: April 2024

The loss of consciousness (LOC) during seizures is one of the most striking features that significantly impact the quality of life, even though the neuronal network involved is not fully comprehended. We analyzed the intracerebral patterns in patients with focal drug-resistant epilepsy, both with and without LOC. We assessed the localization, lateralization, stereo electroencephalography (SEEG) patterns, seizure duration, and the quantification of contacts exhibiting electrical discharge. The degree of LOC was quantified using the Consciousness Seizure Scale. Thirteen patients (40 seizures) with focal drug-resistant epilepsy underwent SEEG. In cases of temporal lobe epilepsy (TLE, 6 patients and 15 seizures), LOC occurred more frequently in seizures with mesial rather than lateral temporal lobe onset. On the other hand, in cases of frontal lobe epilepsy (7 patients; 25 seizures), LOC was associated with pre-frontal onset, a higher number of contacts with epileptic discharge compared to the onset count and longer seizure durations. Our study revealed distinct characteristics during LOC depending on the epileptogenic zone. For temporal lobe seizures, LOC was associated with mesial seizure onset, whereas in frontal lobe epilepsy, seizure with LOC has a significant increase in contact showing epileptiform discharge and a pre-frontal onset. This phenomenon may be correlated with the broad neural network required to maintain consciousness, which can be affected in different ways, resulting in LOC
Rituximab or cyclosporine A for the treatment of membranous nephropathy: economic evaluation of the MENTOR trial
Authors: Kadatz Matthew , Klarenbach Scott , So Helen , Fervenza Fernando C , Cattran Daniel C , Barbour Sean J ,   MENTOR Study Investigators, Fervenza F C , Cattran D C , Appel G , Gipson D , Kretzler M , Rovin B , Fervenza F C , Lieske J C , Leung N , Erickson S B , Radhakrishnan J , Bomback A , Hogan J , Canetta P , Ahn W , Lafayette R , Arora N , Nargund P , Rovin B , Alvarado A , Parikh S , Hebert L A , Aslam N , Porter I , Gipson P , Kretzler M , Plattner B , Gipson D , Mariani L , Garg P , Rao P , Sedor J , O'Toole J , Jefferson J A , Nelson P J , McCarthy E , Yarlagadda S , Jain N , Rizk D , Simon J , Gebreselassie S , Blumenthal S , Beara-Lasic L , Zhdanova O , Thomas L , Cohen I , Keddis M , Sussman A , Thajudeen B , Juncos L , Fulop T , Craici I , Wagner S , Dreisbach A , Monga D , Green D , Mattiazzi A , Nayer A , Thomas D , Barisoni L , Li T , Vijayan A , Cattran D C , Reich H , Hladunewich M , Barbour S , Levin A , Philibert D , Mac-Way F , Desmeules S , Ankawi G , Sethi S , Avila-Casado C , Beanlands H
Published: April 2024

Background and hypothesis

The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health-care payers.

Methods

A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health-care payer with a lifetime time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced-cost biosimilar rituximab.

Results

Rituximab for the treatment of membranous nephropathy was cost effective (assuming a willingness-to-pay threshold of $50 000 per quality-adjusted life year (QALY) gained; in $US 2021) compared with cyclosporine, with an ICER of $8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was $28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favorable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine.

Conclusions

Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.
Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen
Authors: Mozaffari Essy , Chandak Aastha , Chima-Melton Chidinma , Kalil Andre C , Jiang Heng , Lee EunYoung , Der-Torossian Celine , Thrun Mark , Berry Mark , Haubrich Richard , Gottlieb Robert L
Published: April 2024

Background

Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods.

Method

Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice.

Results

Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68–0.83] and 0.83 [0.76–0.90], respectively). This significant mortality benefit endured across the different VOC periods.

Conclusions

Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.
National HIV and HCV Screening Rates for Hospitalized People who Use Drugs Are Suboptimal and Heterogeneous Across 11 US Hospitals
Authors: Westgard Leo Knudsen , Sato Taisuke , Bradford William S , Eaton Ellen F , Pilcher Finlay , Hale Andrew J , Singh Devika , Martin Marlene , Appa Ayesha A , Meyer Jaimie P , Weimer Melissa B , Barakat Lydia A , Felsen Uriel R , Akiyama Matthew J , Ridgway Jessica P , Grussing Emily D , Thakarar Kinna , White Amy , Mutelayi John , Krsak Martin , Montague Brian T , Nijhawan Ank , Balakrishnan Harini , Marks Laura R , Wurcel Alysse G
Published: April 2024

Background

To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD.

Methods

Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations.

Results

Hospitals had average screening rates of 40% for HIV and 32% for HCV, with widespread heterogeneity in screening rates across facilities. State consent laws and opt-out testing policies were not associated with statistically significant differences in HIV screening rates. On average, hospitals that reflexed HCV viral load testing on HCV antibody testing did not have statistically significant differences in HCV viral load testing rates. We found suboptimal testing rates during inpatient encounters for PWUD. As treatment (HIV) and cure (HCV) are necessary to end these epidemics, we need to prioritize understanding and overcoming barriers to testing.
Incidence of Herpes Zoster and Postherpetic Neuralgia and Herpes Zoster Vaccination Uptake in a US Administrative Claims Database
Authors: Marcum Zachary A , Jain Purva , Embry Alan , Arakaki Brent , Estevez Irisdaly , Viscidi Emma
Published: April 2024

Background

The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years.

Methods

This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated.

Results

Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax.

Conclusions

In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk.
Predictors of nutritional recovery time in children aged 6–59 months with severe acute malnutrition in Sofala Province, Mozambique: survival analysis approach
Authors: Victor Audêncio , Antônio Bélio Castro , Gotine Ana Raquel Manuel , Mahoche Manuel , Pedro Xavier Sancho , Silva Rodrigues Osiyallê Akanni , Ferreira Andrêa J F , Rondó Patrícia H
Published: April 2024

Background

Malnutrition is a public health problem that affects physical and psychosocial well-being. It manifests as a rapid deterioration in nutritional status and bilateral edema due to inadequate food intake or illness.

Methods

This study is a retrospective cohort of 1208 children with severe acute malnutrition (SAM) in Sofala Province from 2018 to 2022. It includes hospitalized children aged 6–59 months with SAM and related complications. The dependent variable is recovery, and the independent variables include age, sex of the child, vomiting, dehydration, hypoglycemia, nutritional edema and anthropometry. Survival curves were plotted using the Kaplan–Meier method, and bivariable and multivariable Cox regression analyses were performed.

Results

The crude analysis revealed significant factors for nutritional recovery in children with SAM, including age, weight, height, malaria, diarrhea and dehydration. Children under 24 months had a 28% lower likelihood of recovery. Weight below 6.16 kg decreased the likelihood by 2%, and height above 71.1 cm decreased it by 20%. Conversely, malaria, diarrhea and dehydration increased the likelihood of recovery. However, after adjustment, only diarrhea remained a significant predictor of nutritional recovery.

Conclusion

This study found that diarrhea is a predictor of nutritional recovery in children with SAM.
Euler-Poincaré Formulae for Positive Depth Bernstein Projectors
Authors: Moy Allen , Savin Gordan
Published: April 2024

Work of Bezrukavnikov–Kazhdan–Varshavsky uses an equivariant system of trivial idempotents of Moy–Prasad groups to obtain an Euler–Poincaré formula for the r-depth Bernstein projector. Barbasch–Ciubotaru–Moy use depth-zero cuspidal representations of parahoric subgroups to decompose the Euler–Poincaré presentation of the depth-zero projector. For positive depth r, we establish a decomposition of the Euler–Poincaré presentation of the r-depth Bernstein projector based on a notion of associate classes of cuspidal pairs for Moy–Prasad quotients. We apply these new Euler–Poincaré presentations to obtain decompositions of the resolutions of Schneider–Stuhler and Bestvina–Savin.
‘I couldn’t carry on taking a drug like that’: a qualitative study of patient perspectives on side effects from rheumatology drugs
Authors: Berthelsen Dorthe B , Nielsen Sabrina M , Rasmussen Marianne U , Voshaar Marieke , Richards Pamela , Bartlett Susan J , Hazlewood Glen S , Shea Beverly J , Tugwell Peter , Ellingsen Torkell , Jørgensen Tanja S , Kristensen Salome , Simon Lee S , Christensen Robin , Flurey Caroline A ,   OMERACT Safety Working Group
Published: April 2024

Objectives

There is growing interest in collecting outcome information directly from patients in clinical trials. This study evaluates what patients with rheumatic and musculoskeletal diseases (RMDs) consider important to know about symptomatic side effects they may experience from a new prescription drug.

Methods

Patients with inflammatory arthritis, who had one or more prescribed drugs for their disease for at least 12 months, participated in focus groups and individual interviews. Discussions were analysed using reflexive thematic analysis.

Results

We conducted seven focus groups with 34 participants across three continents. We found four overarching and two underpinning themes. The ‘impact on life’ was connected to participants’ ‘daily life’, ‘family life’, ‘work life’ and ‘social life’. In ‘psychological and physical aspects’ participants described ‘limitation to physical function’, ‘emotional dysregulation’ and ‘an overall mental state’. Extra tests, hospital visits and payment for medication were considered a ‘time, energy and financial burden’ of side effects. Participants explained important measurement issues to be ‘severity’, ‘frequency’ and ‘duration’. Underpinning these issues, participants evaluated the ‘benefit–harm balance’ which includes ‘the cumulative burden’ of having several side effects and the persistence of side effects over time.

Conclusions

In treatment for RMDs, there seems to be an urgent need for feasible measures of patient-reported bother (impact on life and cumulative burden) from side effects and the benefit–harm balance. These findings contribute new evidence in support of a target domain—an outcome that represents the patient voice evaluating the symptomatic treatment-related side effects for people with RMDs enrolled in clinical trials.
Complex Polyploids: Origins, Genomic Composition, and Role of Introgressed Alleles
Authors: Leal J Luis , Milesi Pascal , Hodková Eva , Zhou Qiujie , James Jennifer , Eklund D Magnus , Pyhäjärvi Tanja , Salojärvi Jarkko , Lascoux Martin
Published: April 2024

Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid’s ancestral species, profoundly reshaping the polyploid’s genomic composition. In such complex polyploids, it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history of Betula pubescens (downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence that B. pubescens is the outcome of an autoploid genome doubling event in the common ancestor of B. pendula and its extant sister species, B. platyphylla, that took place approximately 178,000–188,000 generations ago. Extensive hybridization with B. pendula, B. nana, and B. humilis followed in the aftermath of autopolyploidization, with the relative contribution of each of these species to the B. pubescens genome varying markedly across the species’ range. Functional analysis of B. pubescens loci containing alleles introgressed from B. nana identified multiple genes involved in climate adaptation, while loci containing alleles derived from B. humilis revealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.
Bacillus paralicheniformis 809 and Bacillus subtilis 810 support in vitro intestinal integrity under hydrogen peroxide and deoxynivalenol challenges
Authors: Boll Erik J , Copani Giuseppe , Cappellozza Bruno I
Published: April 2024

We designed and conducted two in vitro experiments to evaluate the effects of two Bacillus spp. probiotics on gut barrier integrity using the transepithelial electrical resistance (TEER) assay under two different challenge models. In Exp. 1, intestinal epithelial cells received or not (CON) B. paralicheniformis 809 (BLI) or B. subtilis 810 (BSU) at a rate of 1 × 108 colony forming units (CFU)/transwell. Two hours after treatment application (CON, BLI, or BSU), 5 mM of the reactive oxygen species hydrogen peroxide, mimicking mucosal oxidative stress, was added alone (HYP) or with each of the Bacillus spp. (HYP + BLI or HYP + BSU). In Exp. 2, cells were assigned to the same treatments as in Exp. 1 (CON, BLI, and BSU), or mycotoxin deoxynivalenol (DON), which was added alone or in combination with BLI or BSU, resulting in another two treatments (DON + BLI and DON + BSU). Transepithelial electrical resistance was measured for 14 h postchallenge. In Exp. 1, a treatment × hour interaction was observed for TEER (P < 0.0001). Adding BLI and BSU resulted in greater TEER values vs. CON for most of the experimental period (P < 0.02), whereas HYP reduced mean TEER and area under the curve (AUC), while increasing the amount of sugar that translocated through the monolayer cells (P < 0.001). A treatment × hour interaction was also observed in Exp. 2 (P < 0.0001), as DON led to an immediate and acute drop in TEER that lasted until the end of the experimental period (P < 0.0001). Both BLI and BSU alleviated the DON-induced damaging effects on the integrity of intestinal epithelial cells, whereas both Bacillus spp. alleviated the damage caused by DON alone and the proportion of sugar that translocated through the monolayer cells was not different between CON and DON + BLI (P = 0.14) and DON + BLI and DON + BSU (P = 0.62). In summary, both Bacillus spp. strains (B. paralicheniformis 809 and B. subtilis 810) were able to counteract the damaging effects of the challenge agents, hydrogen peroxide and deoxynivalenol, on gut barrier integrity.
Short term biodistribution and in vivo toxicity assessment of intravenously injected pristine graphene oxide nanoflakes in SD rats
Authors: De Indranil , Singh Rashmika , Kumar Sushil , Singh Srishti , Singh Manohar , Panda Jiban Jyoti , Ghosh Kaushik , Mishra Durga Prasad , Singh Manish
Published: April 2024

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.
Selection of the Dominant Endophytes Based on Illumina Sequencing Analysis for Controlling Bacterial Wilt of Patchouli Caused by Ralstonia solanacearum
Authors: Shi Wenguang , Li Junyan , Xie Siyun , Wang Xing , Zhang Yuxin , Yao Huaxiong , Chen Meiqi , Li Jianbin , Deng Zujun
Published: April 2024

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.
Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study
Authors: Zhang Weiyu , Liu Huixin , Liu Ming , Ying Shi , Yuan Renbin , Zeng Hao , Zhang Zhenting , Han Sujun , Si Zhannan , Hu Bin , Wen Simeng , Xu Pengcheng , Yu Weimin , Chen Hui , Wang Liang , Lin Zhitao , Dai Tao , Lin Yunzhi , Xu Tao
Published: April 2024

Background:

Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.

Methods:

Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ
2 or Fisher’s exact test was used for comparison of categorical variables.

Results:

A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.

Conclusions:

PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.
A simplified treatment algorithm for chronic scrotal content pain syndrome
Authors: Kravchick Sergey , Parekattil Sijo J. , Bratslavsky Gennady , Beamer Matthew R. , Moldwin Robert , Shulman Daniel , Nickel J.Curtis
Published: April 2024

Background

Chronic scrotal content pain (CSCP) is a devastating condition characterized by localized scrotal pain that persists for ≥ 3 months and interferes with daily activities. Approximately 2.5% of all urology outpatient visits are associated with CSCP. General urologists may have difficulty treating these patients because of uncertainties regarding the etiology and pathophysiology of CSCP. Therefore, we aimed to provide a simplified diagnostic and treatment approach for CSCP by subdividing it into distinct categories.

Materials and methods

We systematically reviewed the published literature in the PubMed, MEDLINE, and Cochrane databases for all reports on CSCP diagnosis and treatment using the keywords “chronic scrotal content pain,” “testicular pain,” “orchialgia,” “testicular pain syndrome,” “microdenervation of the spermatic cord,” “post-vasectomy pain syndrome,” “post-inguinal hernia repair pain,” “testialgia,” and “pudendal neuralgia.” This review included only CSCP-related articles published in English language.

Results

We subdivided CSCP syndrome into 5 clinical presentation types, including hyperactive cremasteric reflex, pain localized in the testicles, pain in the testis, spermatic cord, and groin, pain localized in the testicles, spermatic cord, groin, and pubis, and pain in the testicles, spermatic cord/groin, and penis/pelvis. Treatments were adjusted stepwise for each type and section. We included more information regarding the role of pudendal neuroglia in CSCP syndrome and discussed more options for nerve blocks for CSCP. For microsurgical spermatic cord denervation failure, we included treatment options for salvage ultrasound-guided targeted cryoablation, Botox injections, and posterior-inferior scrotal denervation.

Conclusions

Different CSCP subtypes could help general urologists assess the appropriate diagnostic and treatment approaches for scrotal pain management in daily practice.
Design of a shared context-aware assistive robot for personalised aged-care services
Authors: Duthie Nicholas , Ansari Keyvan , Wang Mingzhong , Ray Pradeep Kumar
Published: April 2024

Background:

Sensors, robotics, the Internet of Things (IoT) and data analytics hold considerable potential for enhancing the efficiency of care and health outcomes in the health and aged care sectors. The Australian aged care sector in particular faces significant challenges due to an aging population and outdated technological infrastructure. This article builds upon the foundational research conducted through the collaboration between the University of New South Wales and the University of the Sunshine Coast, as part of the European Union VictoryaHome (VH) project (2014–2016). The VH project, which involved partners from Australia, Norway, Sweden, the Netherlands, and Portugal, aimed to enhance the emotional well-being and security of elderly individuals in their homes. The present study specifically addresses some of the challenges identified in relation to the prohibitively high costs and usability of robots for personalized services in the aged care sector.

Methods:

This paper presents the design and implementation of an affordable service robot specifically developed to offer personalized services to multiple users in aged care facilities. The system utilizes a Raspberry Pi 4 and incorporates functionalities that are tailored to the needs identified through interviews with facility managers and staff.

Results:

We successfully demonstrate tracking of entities within a room-scale environment and the switching of profiles using cost-effective devices. Moreover, by tracking multiple entities simultaneously we were able to achieve powerful context-aware functionality that was seamless to the end-user.

Conclusion:

This study underscores the feasibility and potential benefits of employing low-cost, context-aware service robots in aged care environments.
Sexually transmitted infections in midlife women
Authors: Micks Elizabeth
Published: April 2024

Rates of sexually transmitted infections (STIs) are increasing in all age groups. Although STI incidence decreases with age, midlife women have risk factors that may lead to STI acquisition and underdiagnosis. Clinicians may assume that older women are not sexually active. Although many STIs are asymptomatic, when midlife women do experience vaginal symptoms, they may be erroneously attributed to menopause changes. Clinicians should follow evidence-based screening recommendations provided by the US Preventive Services Task Force and consider STIs in the differential diagnosis of vaginal symptoms. Treatment of STIs in midlife women are guided by the Centers for Disease Control and Prevention’s STI Treatment Guidelines.
Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial
Authors: Shen Jiliang , Zhang Yaping , Zhang Bin , Lu Chen , Cao Jiasheng , Chen Mingyu , Zheng Bin , Yang Jin
Published: April 2024

Aim:

A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model.

Methods:

Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups.

Results:

The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups (P=0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups (P=0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups (P=0.004).

Conclusions:

The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.
Improving Antibiotic Overuse in Primary Care
Authors: Wharton Anestasia , Jerome-D’Emilia Bonnie , Avallone Margaret
Published: April 2024

Purpose

Antibiotic overuse has increased over time related to provider knowledge gaps about best practices, provider perception of patient expectations on receiving an antibiotic, possible pressure to see patients in a timely fashion, and concerns about decreased patient satisfaction when an antibiotic is not prescribed. The Centers for Disease Control and Prevention estimates that up to 30% of antibiotics are inappropriately prescribed in the outpatient setting.

Approach

This quality improvement project consisted of a multimodal approach to decrease inappropriate antibiotic prescribing for viral upper respiratory infections (URIs) by using provider education, passive patient education, and clinical decision support tools based on Centers for Disease Control and Prevention recommendations and the Be Antibiotic Aware tool.

Outcomes

Following implementation, there was an 11% decrease in viral URI antibiotic prescribing, from a rate of 29.33% to 18.33% following the multimodal implementation.

Conclusion

The use of evidence-based education and treatment guidelines was found to decrease inappropriate antibiotic prescribing for patients diagnosed with viral URIs.
Specialty-Specific Trends in Surgery for Apical Pelvic Organ Prolapse Post Vaginal Mesh
Authors: Dutta Rahul , Xu Raymond , Wolff Dylan Thomas , Badlani Gopal Hariram , Matthews Catherine Ann
Published: April 2024

Importance

Since transvaginal mesh (VM) kits for apical pelvic organ prolapse (APOP) were labeled “high-risk” in 2016 and subsequently banned in 2019 by the U.S. Food and Drug Administration, the most common remaining surgical options include abdominal mesh-augmented sacrocolpopexy (AS) and transvaginal native tissue suspension (VN).

Objective

The objective of this study was to determine temporal trends in APOP procedures for urologists and gynecologists.

Study Design

Between 2011 and 2020, the American College of Surgeons National Surgical Quality Improvement Program database was queried for AS, VM, and VN.

Results

There were 26,477 cases of APOP repair (32% AS, 6% VM, 62% VN) included, 9% by urologists. Urologists operated on older (65 vs 61 years) patients with more medical comorbidities. Urologists performed significantly higher proportion of AS (65% vs 29%) and VM (8% vs 6%) relative to VN (27% vs 65%) than gynecologists (P < 0.0001). Transvaginal mesh utilization has decreased over time for both specialties (P < 0.05); nonsignificant trends toward increasing AS (P = 0.1646) in urologists and VN (P = 0.0913) in gynecologists concurrently occurred. Significant independent predictors of the operating surgeon being a urologist were surgery being performed in the latter half of the cohort (2016–2020; odds ratio [OR], 1.22), non-White patient race (OR < 1 for all), a concomitant sling being placed (OR = 0.89), the surgery being VM (OR = 2.95) or AS (OR = 4.36), the patient being older (OR > 1 for each age range), and having a higher frailty index score (OR = 1.16).

Conclusions

Significant differences in APOP repair choices exist between specialties. Urologists operate on older, more medically complex patients while demonstrating a strong preference for mesh-augmented compared with transvaginal native tissue repairs.
Chagas disease: lack of knowledge as a risk factor
Authors: Mas D’Alessandro Nicolás Mario , Blaisten Hernán Daniel , Ferrufino Cristian José , Fernández Boccazzi Julián Matías
Published: April 2024

Chagas disease presents not merely as a medical concern but as a multifaceted socio-environmental health issue demanding diverse approaches. In Argentina, an estimated two million individuals are afflicted with Chagas disease, with 600,000 exhibiting clinical manifestations. This study endeavors to gauge the populace’s knowledge levels in Añatuya, situated northeast of Santiago del Estero, and to compare comprehension levels between Chagas disease patients and non-patients. Employing a cross-sectional epidemiological design, demographic, socio-economic, and medical data were gathered through surveys from individuals aged 18 and above attending local healthcare facilities. Analysis revealed that among 200 patients, 12% exhibited low, 66% intermediate, and 22% high levels of elementary knowledge regarding Chagas disease, nearing optimal understanding for an endemic region. However, statistically significant differences (p < 0.05) in knowledge were observed between Chagas and non-Chagas patients in only three out of ten elementary knowledge questions. Moreover, housing quality, a pivotal risk factor for Triatoma Infestans presence, indicated that 78% resided in improved dwellings, yet 22% lived in high-risk housing, reflecting persistent precarious living conditions susceptible to infestation. Enhanced comprehension of Chagas disease fundamentals and associated risk factors could empower endemic area residents towards proactive well-being practices, advocating for improved living standards and disease management strategies.
Standardising Workforce Cost Estimates Across Australian Jurisdictions: Genomic Testing as a Use Case
Authors: Mordaunt Dylan A
Published: April 2024

Introduction

Labour costs are a key driver of healthcare costs and a key component of economic evaluations in healthcare. We undertook the current study to collect information about workforce costs related to clinical genomic testing in Australia, identifying key components of pay scales and contracts, and incorporating these into a matrix to enable modelling of disaggregated costs.

Methods

We undertook a microcosting study of health workforce labour costs in Australia, from a health services perspective. We mapped the genomic testing processes, identifying the relevant workforce. Data was collected on the identified workforce from publicly available pay scales. Estimates were used to model the total cost from a public health services employer perspective, undertaking deterministic and probabilistic sensitivity analyses.

Results

We identified significant variability in the way in which pay scales and related conditions are both structured and the levels between jurisdictions. The total costs (2023-24 AUD $) ranged from 160,794 (113,848 - 233,350) for administrative staff to 703,206 (548,011 - 923,661) for pathology staff (full-time equivalent). Deterministic sensitivity analysis identified that the base salary accounts for the greatest source of uncertainty, from 24.8% (20.0% - 32.9%) for laboratory technicians to 53.6% (52.8% - 54.4%) for medical scientists.

Conclusion

Variations in remuneration levels and conditions between Australian jurisdictions account for considerable variation in the estimated cost of labour and may contribute significantly to the uncertainty of economic assessments of genomic testing and other labour-intensive health technologies. We outline an approach to standardise the collection and estimation of uncertainty for Australian health workforce costs and provide current estimates for labour costs.
Novel genetic insights into the roles of amino acids in metabolic dysfunction-associated steatotic liver disease
Authors: Liu Jun , Chen Yuxuan , Qian Jin , Cui Ri , Demirkan Ayse , Zheng Yihu
Published: April 2024

Background

Previous research has suggested potential links between amino acids and metabolic dysfunction-associated steatotic liver disease (MASLD), but the precise roles of amino acids in MASLD development are not well understood. This study aimed to obtain insights into the relationships between circulating amino acids and MASLD.

Methods

Utilizing data from the UK Biobank, we examined the observational associations of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Bi-directional two-sample Mendelian randomization (MR) was conducted using genome-wide association study data to investigate the causal relationships between amino acids and MASLD. Multiple MR methods comprising MR-Egger and MR-PRESSO were applied to assess pleiotropy and heterogeneity, and multivariable MR was conducted to evaluate the impacts of body mass index (BMI) on these associations. Survival analysis assessed the link between baseline amino acid levels and the risk of major outcomes.

Results

We identified nine amino acids significantly associated with MASLD in the observational study. The genetic predisposition towards higher leucine (odds ratio (OR) [95% confidence interval (CI)]: 2.1 [1.4, 3.2]), valine (OR [95% CI]: 1.8 [1.3, 2.7]), and alanine (OR [95% CI]: 1.4 [1.1, 1.8]) levels were significantly associated with MASLD. By contrast, the genetic predisposition for increased MASLD risk was significantly associated with phenylalanine (beta = 0.05,p= 4.0×10-4). Further analysis showed that valine may mediate the association between BMI and MASLD, and may also have an exclusive effect on MASLD in addition to the effect of obesity (beta = 1.3,p= 1.9×10-4). Elevated phenylalanine levels in MASLD patients were linked with an increased risk of metabolic dysfunction-associated steatohepatitis (MASH), hepatocellular carcinoma, cirrhosis, heart failure, stroke, and mortality.

Conclusion

We found genetic associations between circulating branched-chain amino acids, particularly leucine and valine, and MASLD, independent of obesity. Phenylalanine was identified as a potential biomarker for MASLD prognostic complications. These results highlight the importance of amino acid metabolism in MASLD as well as suggest new possibilities for research and therapeutic intervention.