bluuebunny/crossref_metadata_2025 huggingface dataset:
Letrozole Pretreatment With Misoprostol Versus Misoprostol Alone For Induction of First Trimesteric Missed Miscarriage A Randomized Controlled Trial
Authors: Moustafa Mohammed Hussein , Shahawy Yasser Mohammed El , Garas Peter Samir
Published: October 2021

Background

Miscarriage or spontaneous abortion is the involuntary termination of pregnancy before 20 weeks of gestation or a fetus born weighting less than 500 grams.

Objective

To compare between the safety and efficacy of two treatment modalities in medical termination of first trimesteric missed miscarriage.

Patients and Methods

This study was conducted at outpatient Obstetric clinic of Ain Shams maternity hospital in the period between June 2017 and December 2018. The patients who were fulfilling the inclusion criteria, were recruited in the study, then an informed consent was taken before starting the trial.

Results

In the total of 88 patients who were recruited in the study, 3 patients dropped from the study, 2 patients from the first group and 1 patient from the second group, so 85 patients were analyzed, the complete abortion rate of the letrozole group was significantly higher than that of the misoprostol only group (83.72% compared to 64.29%).

Conclusion

The use of letrozole pretreatment followed by misoprostol for induction of abortion in the first trimester is associated with higher complete abortion rate than misoprostol only.
Low level Laser Therapy versus Ultrasonic therapy for the Treatment of Shoulder Impingement Syndrome A Systematic Review of randomized controlled trials
Authors: El Tayeb Mahmoud N , Hassan Abrar A , Abuelnaga Yasmeen G , Eid Passant M , Tarkhan Yasmeen M , Fathallah Mahmoud M , Awad Ahmed A , Nabhan Ashraf F
Published: October 2021

Background

Shoulder impingement syndrome is a common cause of shoulder pain in primary health care settings. Many physical modalities of treatment are available in clinical practice, however there is insufficient evidence on their relative effectiveness. This review compares the effectiveness of Low Level Laser Therapy (LLLT) with ultrasonic therapy.

Objectives

To assess the effectiveness of LLLT vs. ultrasonic therapy in patients with subacromial impingement syndrome

Search methods

We searched Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, MEDLINE (Pubmed), Embase, Scopus. We searched trials registries on ClinicalTrials.gov (www.ClinicalTrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal (apps.who.int/trialsearch/). We also hand-searched reference lists of all included primary studies, relevant conference proceedings and academic literature, and relevant systematic reviews (both Cochrane and non Cochrane), to identify additional studies missed from the original electronic searches (e.g., unpublished or in press citations). We did not use date or language restrictions.

Selection criteria

Randomized controlled trials comparing LLLT vs. US therapy in adult patients with subacromial impingement syndrome.

Data collection

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected our primary outcomes information from the trials and assessed the quality of evidence for key outcomes using GRADE.

Results

We included 2 RCTs, contributing 67 participants to our qualitative synthesis. The overall risk of bias is high for both studies. Very low-quality evidence from 1 RCT shows slightly increased mean change in pain severity after LLLT compared to ultrasonic therapy in the short term (3 months) (MD 4.69, 95% CI -5.76 to -3.62).[13]. Very low-quality evidence from 1 RCT shows little to no difference in functional improvement after LLLT compared to ultrasonic therapy in the short term (after 3 months) (MD -0.63, 95% CI -5.53 to 4.27) [13]. No studies investigated Range of Motion in the short term. Verylow certainty evidence showed little to no difference in pain severity and function in the immediate post-treatment phase (up to 1 month). No studies addressed long term follow-up.

conclusion

There is insufficient evidence regarding the difference in effects between LLLT and Ultrasonic therapy for the treatment of shoulder impingement syndrome.
Ultrasound in Evaluation of Subclinical Enthesitis of Extensor Digitorum Tendon and Nail Unit Changes in Psoriasis
Authors: Sherif Nahed Mounir , Ali Elwi Mohamed , El Mallah Reem , Ali Mohamed Sara Samir
Published: October 2021

Background

Subclinical inflammation at entheseal level has been detected in patients with psoriasis without previous history of arthropathy or Psoriatic arthritis (PsA). Ultrasound (US) is a valid and sensitive tool for the assessment of inflammatory involvement at entheseal level in PsA patients.

Objective

To detect subclinical arthritis or enthesitis at distal interphalangeal (DIP) fingers and nail unit changes in psoriatic patient for early detection of PsA

Patients and Methods

This study included 30 adult psoriatic patients and 30 healthy matched controls. All underwent history, clinical examination, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI) score calculation and musculoskeletal US both grey and power Doppler (PD) assessed at enthesis of extensor digitorum tendon insertion at distal phalanx, DIP joints from 2nd to 5th finger bilaterally examined for detection of synovitis and over the nail for morpho-structural evaluation.

Results

Patient’s ages ranged from 18-65 years and controls 20-60 years (mean ±SD 45.07 ± 13.52, 38.37 ± 11.96 respectively), male to female ratio 1:2. DIP joint affection in the form of synovial hypertrophy and effusion with PD was found in 13.3% of cases. Enthesophyte with PD in 56.7% of cases. On comparison between NAPSI score by clinical examination versus US examination, the sensitivity of US was 100%, all cases clinically positive by NAPSI were positively affected by US (20 cases). Also 30% of cases were negative by NAPSI and were positive by US (7cases). Three cases were negative by both NAPSI and US. A significant positive correlation was observed between disease duration and NAPSI Score (r = 0.429, pvalue<0.05), similarly between presence of enthesophyte with PD and PASI Score (r = 0.547, pvalue<0.02).

Conclusion

Detection of subclinical enthesopathy at DIP joint by ultrasound is not infrequent, so it is an important tool for examining enthesis in psoriatic patients. The presence of a high PASI score and long disease duration could be considered as predictive parameters for the presence of psoriatic enthesitis ongoing to arthritis.
Health Risks of Low Dose Of Ionizing Radiation Among Health Care Providers at ain Shams University Hospitals
Authors: Abbas D , Gabal MS , Ez- Elarab HS , El Khazragy NN , Manzour AF
Published: October 2021

Introduction

Ionizing radiation (IR) is an occupational hazard that can induce many health risks on exposed health care workers (HCWs). However, the health risks of low dose (below 100mSv) are controversial due to a lack of direct evidence on human.

Aim of work

To identify the health risks of exposure to low dose of ionizing radiation and its effect on general health status and to assess oxidative stress status of health care workers (HCWs) exposed to IR at Ain Shams University hospitals.

Materials and methods

A comparative cross-sectional study was conducted including 50 HCWs from different departments of Ain Shams University hospitals: exposed group (exposed to IR for at least I year) (No = 25) and matched unexposed control group (No = 25). Both groups were interviewed using a structured questionnaire. Assessment of health care workers' oxidative stress status was done for both groups by measure level of plasma malondialdehyde (MDA) level as biomarker for lipid peroxidation. Complete blood count was done for both groups. Recording readings of personal exposure to IR by badge film dosimeter after approval from workplace authority was also done.

Results

Regarding general health status and wellbeing of workers, most of exposed group had perception of average health status, while most of unexposed group had perception of good health status. A significantly higher sickness absenteeism during the last 6 months was found among the exposed group and a significant adverse health effects, were recorded among exposed group compared to control group as hair fall, musculoskeletal pain, pain in upper abdomen, constipation, decreased visual acuity, in addition to easily agitated. During the last 30 days exposed group had significantly higher frequencies of GIT disturbances and common cold or infections in comparison to unexposed group. The results showed that IR exposed group had the more oxidative stress status (higher level of plasma MDA) than unexposed group with significant difference (p value =0.014). Results showed also that the Mean Corpuscular Hemoglobin (MCH), Absolute lymphocyte and monocyte counts were significantly lower while relative basophile % was significantly higher among exposed group in comparison to unexposed group (although all parameters were within normal range in both groups).

Conclusion

Exposure to IR -even in small dose- may lead to significant health complains (adverse health effects), increase oxidative stress status and may affect general health status among exposed group compared to the non-exposed one.

Recommendations

Personal monitoring for ionizing radiation, periodic medical examination, and increasing level of protection for exposed workers are of utmost importance.
Reporting Medication Errors and Drug Therapy Problems Through the Egyptian National Electronic Reporting System in 56 Governmental Hospitals during 2019
Authors: AbdulAziz Hebatalla Mohamed , Mostafa Aya , Hakim Sally Adel , Moustafa Moustafa El- Houssine
Published: October 2021

Introduction

Several countries have adopted national reporting systems of medication errors such as in the UK and the USA. Egypt has a new national reporting system of medication error (MEs) & drug therapy problems (DTPs), the NO HARMe (the National Office for Handling And Reduction of Medication errors) since October 2017.

Objectives

To determine the most common types of MEs and DTPs encountered by clinical pharmacists as the NO HARMe users in governmental hospitals.

Methodology

We conducted a cross-sectional survey using a self-administered online questionnaire in fifty-six governmental hospitals where clinical pharmacists use the NO HARMe, from October to December 2019.

Results

Most (96%) of the 206 participating clinical pharmacists were females with a mean age of 32.8 years (SD 4.32). The most common departments where participants worked are adult ICU (32.5%), neonatal ICU (14.6%), pediatric ICU (7%), and internal medicine (5%). The most common types of DTPs & MEs reported by clinical pharmacists were inappropriate doses or dosing intervals (38.3%), drugs with no valid indications (25.2%), antibiotics without indication (17.5%), and inappropriate selection of an antibiotic (13.6%).

Conclusion

Medication errors in drug dosing are prevalent in the hospitals included in this study. Also, drugs that are prescribed without need, while errors in antibiotics were very common in many hospitals either prescribed for no need or selected inappropriately.
Pulled Diversification Rates, Lineages-Through-Time Plots, and Modern Macroevolutionary Modeling
Authors: Helmstetter Andrew J , Glemin Sylvain , Käfer Jos , Zenil-Ferguson Rosana , Sauquet Hervé , de Boer Hugo , Dagallier Léo-Paul M J , Mazet Nathan , Reboud Eliette L , Couvreur Thomas L P , Condamine Fabien L
Published: October 2021

Estimating time-dependent rates of speciation and extinction from dated phylogenetic trees of extant species (timetrees), and determining how and why they vary, is key to understanding how ecological and evolutionary processes shape biodiversity. Due to an increasing availability of phylogenetic trees, a growing number of process-based methods relying on the birth–death model have been developed in the last decade to address a variety of questions in macroevolution. However, this methodological progress has regularly been criticized such that one may wonder how reliable the estimations of speciation and extinction rates are. In particular, using lineages-through-time (LTT) plots, a recent study has shown that there are an infinite number of equally likely diversification scenarios that can generate any timetree. This has led to questioning whether or not diversification rates should be estimated at all. Here, we summarize, clarify, and highlight technical considerations on recent findings regarding the capacity of models to disentangle diversification histories. Using simulations, we illustrate the characteristics of newly proposed “pulled rates” and their utility. We recognize that the recent findings are a step forward in understanding the behavior of macroevolutionary modeling, but they in no way suggest we should abandon diversification modeling altogether. On the contrary, the study of macroevolution using phylogenetic trees has never been more exciting and promising than today. We still face important limitations in regard to data availability and methods, but by acknowledging them we can better target our joint efforts as a scientific community. [Birth–death models; extinction; phylogenetics; speciation.]
Screening of Early Maturing Soybean Accessions for Resistance Against HG Type 2.5.7 of Soybean Cyst Nematode Heterodera glycines
Authors: Acharya Krishna , Yan Guiping
Published: October 2021

Soybean cyst nematode (SCN; Heterodera glycines) is one of the devastating soybean pests worldwide, including in the United States. Resistant cultivars combined with crop rotation are the primary methods for managing this nematode. SCN is known to have genetically diverse populations and can develop new virulent forms over time due to the continuous planting of cultivars derived from same source of resistance. Thus, identifying novel SCN resistant sources is of paramount importance for soybean breeding for nematode resistance. In this study, we screened 149 early maturity soybean [Glycine max (L.)] accessions for resistance to SCN HG type 2.5.7, which is one of the prevalent virulent SCN populations in North Dakota. SCN white females were extracted from individual plants of each accession after 35 days of growth in greenhouse conditions. The females were counted to determine a female index (FI = [average number of females on a tested accession/average number of females in Barnes, a susceptible soybean check] × 100). The resistance response of each soybean accession was categorized as resistant, moderately resistant, moderately susceptible, and susceptible. Of the 149 soybean accessions tested, only 13 were resistant in both runs of the experiments. The majority of screened soybean accessions were susceptible or moderately susceptible to the SCN HG type 2.5.7. The resistant soybean accessions identified in this study have the potential to be used in breeding SCN-resistant cultivars after further elucidation of the resistance genes or loci.
Understanding the course of COVID-19-induced pneumomediastinum
Authors: Panico Rocco , Cai Jenny , Butts Christopher A. , To Jennifer Q.
Published: October 2021

Since its discovery, COVID-19 has infected nearly 112 million people and caused about 2.5 millions deaths worldwide. Our understanding of the clinical presentation and complications of COVID-19 is still evolving. Bilateral pulmonary ground-glass opacities on imaging have become characteristic in the diagnosis of COVID-19, but pneumomediastinum has now also been reported in some patients with COVID-19. Reports on the overall prognosis for these patients are conflicting and little information exists regarding long-term complications. This article describes the clinical course of a patient who did not need mechanical ventilation but developed spontaneous pneumomediastinum.
Validity of Pulse Oximetry-derived Peripheral Perfusion Index in Pain Assessment in Critically Ill Intubated Patients
Authors: Abdelhakeem Amr K. , Amin Alya , Hasanin Ahmed , Mukhtar Ahmed , Eladawy Akram , Kassem Sahar
Published: October 2021

Objectives:

Evaluation of pain in critically ill intubated patients is difficult and subjective. This study aimed to evaluate the accuracy of oximetry-derived peripheral perfusion index (PPI) in pain assessment in critically ill intubated patients using the behavioral pain scale (BPS) as a reference.

Materials and Methods:

This prospective observational study included 35 adult mechanically ventilated surgical patients during their first 2 postoperative days in the intensive care unit. Values of PPI, BPS, Richmond Agitation Sedation Scale (RASS), heart rate, and blood pressure were obtained before and after a standard painful stimulus (changing the patient position) and the ratio between the second and the first reading was calculated to determine the change (Δ) in all variables. The outcomes were the correlation between ΔBPS and ΔPPI as well as other hemodynamic parameters. The ability of the PPI to detect pain (defined as BPS ≥6) was analyzed using the area under receiver operating characteristic curve.

Results:

Paired readings were obtained from 35 patients. After the standard painful stimulus, the PPI decreased while the BPS and the Richmond agitation sedation scale increased. The Spearman correlation coefficient (95% confidence interval) between Δ PPI and Δ BPS was 0.41 (0.09-0.65). PPI values showed poor accuracy in detecting pain with area under receiver operating characteristic curve (95% confidence interval): 0.65 (0.53-0.76), with best cutoff value of ≤2.7.

Conclusion:

The PPI decreased after application of a standard painful stimulus in critically ill intubated patients. ∆PPI showed a low correlation with ∆BPS, and a PPI of ≤2.7 showed a low ability to detect BPS ≥6. Therefore, PPI should not be used for pain evaluation in critically ill intubated surgical patients.
Effects of the Close Collaboration With Parents Intervention on the Quality of Family-Centered Care in NICUs
Authors: Toivonen Mirka , Lehtonen Liisa , Ahlqvist-Björkroth Sari , Axelin Anna
Published: October 2021

Background:

Systematic training for the neonatal staff to support parents' active involvement is lacking. There is little information about the effectiveness of educational interventions.

Purpose:

To evaluate the effects of an educational intervention to neonatal staff on the quality of family-centered care from the perspectives of parents and nurses.

Methods:

A quasi-experimental before and after study was carried out in 5 Finnish neonatal units in 2014-2018. Data were collected using the DigiFCC-tools with a 7-point Likert scale. Thirty-one fathers and 53 mothers were recruited before the intervention and 21 fathers and 61 mothers after the intervention. They answered 1 question every evening until their infants' discharge. Each nurse answered 1 corresponding question after every shift, during the same period before and after the intervention. Before the intervention 3239 responses and after the intervention 3092 responses were received from nurses.

Results:

The fathers' total score and the score indicating “Shared decision making” were higher after the intervention than before the intervention. The mothers' total score did not differ between the 2 time periods. The nurses' total score was higher after the intervention than before the intervention. Of the individual items, higher scores were found for “Active listening,” “Parents' trust in the nurse,” and “Emotional support.”

Implications for Practice:

Developing the staff's negotiating and active listening skills facilitates better support for parents during infants' intensive care.

Implications for Research:

Family-centered care interventions such as Close Collaboration with Parents should be studied in randomized controlled trials, also including child outcomes.
Mesenteric Excision and Exclusion for Ileocolic Crohn’s Disease: Feasibility and Safety of an Innovative, Combined Surgical Approach With Extended Mesenteric Excision and Kono-S Anastomosis
Authors: Holubar Stefan D. , Gunter Rebecca L. , Click Benjamin H. , Achkar Jean-Paul , Lightner Amy L. , Lipman Jeremy M. , Hull Tracy L. , Regueiro Miguel , Rieder Florian , Steele Scott R.
Published: October 2021

INTRODUCTION:

Ileocolic resection for Crohn’s disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn’s disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion.

TECHNIQUES:

This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn’s disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented.

RESULTS:

Twenty-two patients with ileocolic Crohn’s disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak.

CONCLUSIONS:

Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn’s disease.
Biomechanical comparisons of different diagonal screw designs in a novel embedded calcaneal slide plate
Authors: Wang Shun-Ping , Lai Wei-Yi , Lin Yi-Yin , Lin Tzu-Wei , Tsai Ming-Tzu , Yang Yi-Ping , Hsu Cheng-En , Chen Chao-Ping , Lee Cheng-Hung , Su Kuo-Chih
Published: October 2021

Background:

Medial displacement calcaneal osteotomy (MDCO) is frequently used for the surgical correction of flatfoot. This study aims to investigate the biomechanical effect of the different diagonal screw design on a novel-designed embedded calcaneal plate for MDCO using finite element analysis (FEA), mechanical test and digital image correlation (DIC) measurement.

Methods:

Four groups according to the varied implanted plate were set as control group (Group 1), non-diagonal screw (Group 2), one-diagonal screw (Group 3), and two-diagonal screws groups (Group 4). For FEA, A 450 N load was applied to on the anterior process of the calcaneus from top to bottom. Observational indices included the stress on the cortical and cancellous bone of the calcaneus surrounding the implant, the plate itself as well as screws, and the displacement of the overall structure. In addition, this study also used in vitro biomechanics test to investigate the stiffness of the structure after implantation, and used DIC to observe the displacement of the calcaneus structure after external force.

Results:

Under a simulated load in FEA, there are significant overall instability and high stress concentration on the calcaneal surrounding host bone and the plate/screws system, respectively, in group 2 compared with other groups. Regard to the mechanical testing with DIC system, significant increased rotation stability, maximum force and stiffness with the addition of diagonal screws. In comparison to Group 2, the increase of 112% and 157% in maximum force as well as 104% and 176% in stiffness were found in Group 3 and 4, respectively.

Conclusion:

For reducing stress concentration and enhancing overall stability, more than one-diagonal screw design is recommended and two-diagonal screws design will be superior. This study provided biomechanical references for further calcaneal implants design to prevent clinical failure after MDCO.
Prevention of Occupational Heat-Related Illnesses
Authors: Tustin Aaron , Sayeed Yusef , Berenji Manijeh , Fagan Kathleen , McCarthy Ronda B. , Green-McKenzie Judith , McNicholas James , Onigbogi Charles Babajide , Perkison William Brett , Butler James W.
Published: October 2021

High ambient temperatures and strenuous physical activity put workers at risk for a variety of heat-related illnesses and injuries. Through primary prevention, secondary prevention, and treatment, OEM health providers can protect workers from the adverse effects of heat. This statement by the American College of Occupational and Environmental Medicine provides guidance for OEM providers who serve workers and employers in industries where heat exposure occurs.
Polyuria due to Pressure Natriuresis in Venoarterial Extracorporeal Membrane Oxygenation
Authors: Rosen Raphael J. , Stevens Jacob S. , Canetta Pietro A. , Siddall Eric
Published: October 2021

We report a case of a 40-year-old woman who developed profound polyuria (>25 L urine output) immediately after initiation of venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Investigations into the cause determined the polyuria was due to marked natriuresis (>85 g of sodium excreted in 1 day). This natriuresis persisted despite low cardiac filling pressures and high-negative ECMO venous pressures, suggesting clinical hypovolemia due to pressure natriuresis from locally high pressures at the renal artery due to arterial ECMO inflow. As ECMO flows were decreased, polyuria and natriuresis resolved. To our knowledge, this is the first description of VA-ECMO–associated salt wasting.
SARS-CoV-2 Infection Among People Living With HIV Compared With People Without HIV: Survey Results From the MACS-WIHS Combined Cohort Study
Authors: D'Souza Gypsyamber , Tong Weiqun , Gustafson Deborah , Alcaide Maria L. , Lahiri Cecile D. , Sharma Anjali , French Audrey L. , Palella Frank J. , Kempf Mirjam-Colette , Mimiaga Matthew J. , Ramirez Catalina , Kassaye Seble , Rinaldo Charles R. , Brown Todd T. , Tien Phyllis C. , Adimora Adaora A.
Published: October 2021

Background:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) symptoms among people living with HIV (PLWH) are not well described.

Setting:

Longitudinal survey within the MACS/WIHS Combined Cohort Study (MWCCS) of PLWH compared with similar HIV-seronegative (SN) individuals.

Methods:

Telephone-administered survey of MWCCS participants at 13 clinical research sites across the United States addressing COVID-19 symptoms, SARS-CoV-2 testing, and pandemic impact on social distancing and antiretroviral therapy (ART) use. Primary data collection occurred during May (wave 1), June–July (wave 2), and August–September, 2020 (wave 3).

Results:

One-third of MWCCS participants were tested for SARS-CoV-2 infection; 10% was tested ≥2 times. Similar proportions of PLWH and SN participants were tested, but SARS-CoV-2 positivity was higher among PLWH than among SN individuals (9.4% vs 4.8%, P = 0.003). Odds of SARS-CoV-2 positivity remained higher among PLWH after adjusting for age, sex, race/ethnicity, and study site (adjusted odds ratio = 2.0, 95% confidence interval = 1.2 to 3.2). SARS-CoV-2 positivity was not associated with CD4 cell counts among PLWH. Among SARS-CoV-2 positive participants, 9% had no symptoms, 7% had 1–2 mild symptoms, and 84% had ≥3 symptoms. Most of the (98%) participants reported physical distancing during all survey waves; self-reported ART adherence among PLWH was not adversely affected during the pandemic compared with the previous year (similar adherence in 89% of participants, improved in 9% of participants, and decreased in 2% of participants).

Conclusions:

Despite similar SARS-CoV-2 testing and physical distancing profiles by HIV serostatus among MWCCS participants, PLWH who reported SARS-CoV-2 testing were more likely to have a positive test result. Additional studies are needed to determine whether and why PLWH are at increased risk of SARS-CoV-2 infection.
225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer
Authors: Sanli Yasemin , Kuyumcu Serkan , Simsek Duygu Has , Büyükkaya Fikret , Civan Caner , Isik Emine Goknur , Ozkan Zeynep Gozde , Basaran Mert , Sanli Oner
Published: October 2021

Purpose

Prostate-specific membrane antigen (PSMA)–targeted therapies are among the current promising treatments. We present our preliminary results on the use of 225Ac-PSMA therapy in patients with metastatic castration-resistant prostate cancer as a single center.

Methods

Twelve advanced stage metastatic castration-resistant prostate cancer patients who received 225Ac-PSMA therapy were recruited in this retrospective study. Patients were treated with 225Ac-PSMA therapy every 8 weeks, and prostate-specific antigen (PSA) response was analyzed. Meanwhile, overall survival (OS) and progression-free survival (PFS) were estimated. Hematological and nonhematological adverse effects were recorded before and at 8 weeks after the last treatment cycle.

Results

In total, 25 cycles of 225Ac-PSMA were administered to 12 patients. The pretreatment median PSA level was 129 ng/mL. After the first cycle of therapy, any PSA response was observed in 9 of 12 patients, whereas 6 of them had biochemical response of >50%. Four of 12 patients reached the best PSA response after the first treatment cycle, whereas 3 patients after the second and 2 patients after the third cycle. The median PFS and OS were 4 and 10 months, respectively. For patients with any PSA response after the first cycle, OS was found to be higher despite without any statistical significance (10 vs 4 months; P = 0.301) when compared with the nonresponsive group. No significant difference was encountered in terms of adverse effect in the pretreatment and posttreatment era.

Conclusions

Our preliminary results are encouraging, especially patients who had PSA response after the first cycle of 225Ac-PSMA therapy.
Distinguishing between models of mammalian gene expression: telegraph-like models versus mechanistic models
Authors: Braichenko Svitlana , Holehouse James , Grima Ramon
Published: October 2021

Two-state models (telegraph-like models) have a successful history of predicting distributions of cellular and nascent mRNA numbers that can well fit experimental data. These models exclude key rate limiting steps, and hence it is unclear why they are able to accurately predict the number distributions. To answer this question, here we compare these models to a novel stochastic mechanistic model of transcription in mammalian cells that presents a unified description of transcriptional factor, polymerase and mature mRNA dynamics. We show that there is a large region of parameter space where the first, second and third moments of the distributions of the waiting times between two consecutively produced transcripts (nascent or mature) of two-state and mechanistic models exactly match. In this region: (i) one can uniquely express the two-state model parameters in terms of those of the mechanistic model, (ii) the models are practically indistinguishable by comparison of their transcript numbers distributions, and (iii) they are distinguishable from the shape of their waiting time distributions. Our results clarify the relationship between different gene expression models and identify a means to select between them from experimental data.
Analysis of mouse faecal dysbiosis, during the development of cachexia, induced by transplantation with Lewis lung carcinoma cells
Authors: de Maria Yara N. L. F. , Aciole Barbosa David , Menegidio Fabiano B. , Santos Kaltinaitis B. N. H. , Humberto Ana Carolina , Alencar Valquíria C. , Silva Juliana F. S. , Costa de Oliveira Regina , Batista Jr Miguel L. , Nunes Luiz R. , Jabes Daniela L.
Published: October 2021

Cachexia (CC) is a complex wasting syndrome that significantly affects life quality and life expectancy among cancer patients. Original studies, in which CC was induced in mouse models through inoculation with BaF and C26 tumour cells, demonstrated that CC development correlates with bacterial gut dysbiosis in these animals. In both cases, a common microbial signature was observed, based on the expansion of

Enterobacteriaceae

in the gut of CC animals. However, these two types of tumours induce unique microbial profiles, suggesting that different CC induction mechanisms significantly impact the outcome of gut dysbiosis. The present study sought to expand the scope of such analyses by characterizing the CC-associated dysbiosis that develops when mice are inoculated with Lewis lung carcinoma (LLC) cells, which constitutes one of the most widely employed mechanisms for CC induction. Interestingly,

Enterobacteriaceae

expansion is also observed in LLC-induced CC. However, the dysbiosis identified herein displays a more complex pattern, involving representatives from seven different bacterial phyla, which were consistently identified across successive levels of taxonomic hierarchy. These results are supported by a predictive analysis of gene content, which identified a series of functional/structural changes that potentially occur in the gut bacterial population of these animals, providing a complementary and alternative approach to microbiome analyses based solely on taxonomic classification.
Carpenter Bee Thorax Vibration and Force Generation Inform Pollen Release Mechanisms During Floral Buzzing
Authors: Jankauski Mark , Casey Cailin , Heveran Chelsea , Busby M. Kathryn , Buchmann Stephen
Published: October 2021

Approximately 10% of flowering plant species conceal their pollen within tube-like poricidal anthers. Bees extract pollen from poricidal anthers via floral buzzing, a behavior during which they apply cyclic forces by biting the anther and rapidly contracting their flight muscles. The success of pollen extraction during floral buzzing relies on the direction and magnitude of the forces applied by the bees, yet these forces and forcing directions have not been previously quantified. In this work, we developed an experiment to simultaneously measure the directional forces and thorax kinematics produced by carpenter bees (Xylocopa californica) during defensive buzzing, a behavior regulated by similar physiological mechanisms as floral buzzing. We found that the buzzing frequencies averaged about 130 Hz and were highly variable within individuals. Force amplitudes were on average 170 mN, but at times reached nearly 500 mN. These forces were 30 – 80 times greater than the weight of the bees tested. The two largest forces occurred within a plane formed by the bees’ flight muscles. Force amplitudes were moderately correlated with thorax displacement, velocity and acceleration amplitudes but only weakly correlated with buzzing frequency. Linear models developed through this work provide a mechanism to estimate forces produced during non-flight behaviors based on thorax kinematic measurements in carpenter bees. Based on the buzzing frequencies, individual bee’s capacity to vary buzz frequency and predominant forcing directions, we hypothesize that carpenter bees leverage vibration amplification to increase the deformation of poricidal anthers, and hence the amount of pollen ejected.
A Genetic Platform for Functionally Profiling Odorant Receptors Ex Vivo Using Olfactory Cilia
Authors: Omura Masayo , Takabatake Yukie , Lempert Eugene , Benjamin-Hong Sigi , D’Hulst Charlotte , Feinstein Paul
Published: October 2021

The molecular basis for odor perception in humans remains an enigma as odorant receptors (ORs) are notoriously difficult to study outside of their native environment. Efforts toward OR expression and functional profiling have been met with limited success due to poor efficiency of in vitro cell surface expression. Olfactory cilia are known to contain all components of the olfactory signal transduction machinery and can be placed into an ex vivo well-plate assay to rapidly measure robust, reproducible odor-specific responses. We now describe the isolation of cilia from mouse nose bioreactors for two human ORs, OR1A1 and OR5AN1, and reveal 10-100 fold more sensitivity compared to previously reported assays. A single animal can produce up to 4,000 384-well assay wells, and isolated olfactory cilia can be stored frozen and thus preserved. This pipeline offers a sensitive, highly scalable ex vivo odor screening platform that opens the door for decoding human olfaction.

One Sentence Summary

olfactory-cilia based odor screening platform.
Different methods for niche and fitness differences computation offer contrasting explanations of species coexistence
Authors: Spaak Jurg W. , Ke Po-Ju , Letten Andrew D. , De Laender Frederik
Published: October 2021

In modern coexistence theory, species coexistence can either arise via stabilizing mechanisms that increase niche differences or equalizing mechanisms that reduce fitness differences. Having a common currency for interpreting these mechanisms is essential for synthesizing knowledge across different studies and systems. Several methods for quantifying niche and fitness differences exist, but it remains unknown to what extent these methods agree on the reasons why species coexist. Here, we apply four common methods to quantify niche and fitness differences to one simulated and two empirical data sets. We ask if different methods result in different insights into what drives species coexistence. We find that different methods disagree on the effects of resource supply rates (simulated data), and of plant traits or phylogenetic distance (empirical data), on niche and fitness differences. More specifically, these methods often do not agree better than expected by chance. We argue for (1) a better understanding of what connects and sets apart different methods, and (2) the simultaneous application of multiple methods to enhance a more complete insight into why species coexist.
Beyond the reach of homology: successive computational filters find yeast pheromone genes
Authors: Srikant Sriram , Gaudet Rachelle , Murray Andrew W.
Published: October 2021

The mating of fungi depends on pheromones that mediate communication between two mating types. Most species use short peptides as pheromones, which are either unmodified (e.g., α-factor in Saccharomyces cerevisiae) or C-terminally farnesylated (e.g., a-factor in S. cerevisiae). Peptide pheromones have been found by genetics or biochemistry in small number of fungi, but their short sequences and modest conservation make it impossible to detect homologous sequences in most species. To overcome this problem, we used a four-step computational pipeline to identify candidate a-factor genes in sequenced genomes of the Saccharomycotina, the fungal clade that contains most of the yeasts: we require that candidate genes have a C-terminal prenylation motif, are fewer than 100 amino acids long, contain a proteolytic processing motif upstream of the potential mature pheromone sequence, and that closely related species contain highly conserved homologs of the potential mature pheromone sequence. Additional manual curation exploits the observation that many species carry more than one a-factor gene, encoding identical or nearly identical pheromones. From 332 fungal genomes, we identified strong candidate pheromone genes in 238 genomes, covering 13 clades that are separated from each other by at least 100 million years, the time required for evolution to remove detectable sequence homology. For one small clade, the Yarrowia, we demonstrated that our algorithm found the a-factor genes: deleting all four related genes in the a-mating type of Yarrowia lipolytica prevents mating.
MotifBoost: k-mer based data-efficient immune repertoire classification method
Authors: Katayama Yotaro , Kobayashi Tetsuya J.
Published: October 2021

The repertoire of T cell receptors encodes various types of immunological information. Machine learning is indispensable for decoding such information from repertoire datasets measured by next-generation sequencing. In particular, the classification of repertoires is the most basic task, which is relevant for a variety of scientific and clinical problems. Supported by the recent appearance of large datasets, efficient but data-expensive methods have been proposed. However, it is unclear whether they can work efficiently when the available sample size is severely restricted as in practical situations. In this study, we demonstrate that the their performances are impaired catastrophically below critical sample sizes. To overcome this, we propose MotifBoost, which exploits the information of short motifs of TCRs. MotifBoost can perform the classification as efficiently as a deep learning method on large datasets while providing more stable and reliable results on small datasets. We also clarify that the robustness of MotifBoost can be attributed to the efficiency of motifs as representation features of repertoires. Finally, by comparing predictions of these methods, we show that the whole sequence identity and sequence motifs encode partially different information and that a combination of such complementary information is necessary for further development of repertoire analysis.
Single-cell RNA-seq analysis reveals aberrant CSF1 expression in disease-causing synovial fibroblasts of pigmented villonodular synovitis
Authors: Tang Yiyong , Ma Mengjun , Mi Rujia , Liu Wenzhou , Hou Jingyi , Feng Yanjie , Zhang Meijun , Yu Menglei , Li Fangqi , Song Yihui , Lu Yixuan , Yan Yan , Yang Rui
Published: October 2021

Objectives

Although the role of the CSF1/CSF1R axis in pigmented villonodular synovitis (PVNS) has been confirmed, the cells that express CSF1 and CSF1R and the underlying mechanism remain unclear. Single-cell RNA sequencing (scRNA-seq) of PVNS obtained through biopsies depicted the cellular diversity of PVNS, revealed specific CSF1/CSF1R-expressing cells and further identified novel gene expression that is associated with the development of PVNS.

Methods

scRNA-seq was performed on tissues obtained from the 6 biopsies of 3 patients with PVNS. Flow cytometry, immunofluorescence and western blot validated the transcriptional results, while co-culture systems revealed the cross talk between fibroblasts and macrophages.

Results

8 subsets of fibroblasts and 5 subsets of macrophages were identified from the synovium of patients with PVNS and were found to be related to distinct signaling pathways. The cellular components of localized and diffuse PVNS are overall similar. Moreover, the synovium and nodule of PVNS share similar composition. The specific cells expressing CSF1/CSF1R were also identified. Other than that, unique CXCL12+CSF1+ fibroblasts were revealed to attract macrophages as disease-causing synovial fibroblasts, leading to the formation of masses in PVNS.

Conclusions

PVNS consists of macrophages, fibroblasts, T cells, endothelial cells and mast cells. Among them, the CSF1-expressing fibroblasts appeared to be tumor-like cells that attract macrophages, subsequently forming tumor-like mass in PVNS. This paves the path for novel treatments of PVNS by targeting CXCL12+CSF1+ fibroblasts and the CXCL12-CXCR4 axis.
Genome graphs detect human polymorphisms in active epigenomic state during influenza infection
Authors: Groza Cristian , Chen Xun , Pacis Alain , Simon Marie-Michelle , Pramatarova Albena , Aracena Katherine A. , Pastinen Tomi , Barreiro Luis B. , Bourque Guillaume
Published: October 2021

Genetic variants, including mobile element insertions (MEIs), are known to impact the epigenome. We hypothesized that the use of a genome graph, which encapsulates genetic diversity, could reveal missing epigenomic signal. Given the contributions of mobile elements to the evolution of primate innate immunity, we tested this in monocyte-derived macrophages obtained from 35 individuals before and afterInfluenzavirus infection. After characterizing genetic variants in this cohort using linked-reads, including 5140 Alu, 316 L1, 94 SVAs and 48 ERVs, we incorporated them into a genome graph. Mapping epigenetic data to this graph revealed 2.5%, 3.0% and 2.3% novel peaks for H3K4me1 and H3K27ac ChIP-seq and ATAC-seq respectively. Notably, using a genome graph also modified quantitative trait loci estimates and we observed 375 polymorphic MEIs in active epigenomic state. For example, we found an AluYh3 polymorphism whose chromatin state changed after infection and that was associated with the expression ofTRIM25, a gene that restricts influenza RNA synthesis. Our results demonstrate that graph genomes can reveal regulatory regions that would have been overlooked by other approaches.
Loss of the GARP but not EARP protein complex drives Golgi sterol overload during dendrite remodeling
Authors: O’Brien Caitlin , Younger Susan H. , Jan Lily Yeh , Jan Yuh Nung
Published: October 2021

Membrane trafficking is essential for sculpting neuronal morphology. The GARP and EARP complexes are conserved tethers that regulate vesicle trafficking in the secretory and endolysosomal pathways, respectively. Both complexes contain the Vps51, Vps52, and Vps53 proteins, and a complex-specific protein: Vps54 in GARP and Vps50 in EARP. In Drosophila, we find that both complexes are required for dendrite morphogenesis during developmental remodeling of multidendritic class IV da (c4da) neurons. Having found that sterol accumulates at the trans-Golgi network (TGN) in Vps54KO/KO neurons, we investigated genes that regulate sterols and related lipids at the TGN. Overexpression of oxysterol binding protein (Osbp) or knockdown of the PI4K four wheel drive (fwd) exacerbates the Vps54KO/KO phenotype, whereas eliminating one allele of Osbp rescues it, suggesting that excess sterol accumulation at the TGN is, in part, responsible for inhibiting dendrite regrowth. These findings distinguish the GARP and EARP complexes in neurodevelopment and implicate vesicle trafficking and lipid transfer pathways in dendrite morphogenesis.