bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Fidelity in a Randomized Controlled Trial of Cognitive Behavioral Therapy for Insomnia in Heart Failure
Authors: O’Connell Meghan , Iennaco Joanne DeSanto , Linsky Sarah , Jeon Sangchoon , Conley Samantha , Gaiser Edward , Redeker Nancy S.
Published: August 2022

Background

Cognitive behavioral therapy for insomnia (CBT-I) is an efficacious treatment for people with chronic insomnia, including those with heart failure (HF). Treatment fidelity evaluation is needed to ensure study validity and reliability.

Objective

To apply the National Institutes of Health Behavioral Change Consortium framework to ensure adequate treatment fidelity in a randomized controlled trial of CBT-I for people with stable HF.

Methods

We describe strategies to ensure treatment fidelity in study design, provider training, and treatment delivery. We measured treatment receipt (observation and self-report) and enactment of CBT-I strategies (self-report and actigraphy). We used the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS) and the Sleep Disturbance Questionnaire (SDQ) to indicate sleep-related beliefs and cognitions. We computed descriptive statistics for demographic characteristics, treatment receipt, and enactment variables. We compared baseline and post-intervention dichotomous sleep behaviors using the two-sided Wilcoxon Rank Sum Test. We calculated the root mean square of successive difference (RMSSD) in time of sleep onset and midpoint (actigraphy) to indicate day-by-day variability in bed and wake times.

Results

Most participants completed the CBT-I intervention and follow-up assessments and attended each group or make-up session. The majority correctly computed their sleep efficiency and completed the homework. Most participants used the sleep tracker and reported using strategies to improve their sleep schedules. There was a significant decrease in actigraph-measured light intensity during the 30 min and 1 hr before bedtime between baseline and post-intervention and no statistically significant changes in light intensity after waking or in nap frequency. Most of those who woke during the night got out of bed, consistent with recommendations. There were significant improvements on all of the DBAS items and total score and all but one item on the SDQ.

Discussion

Preserved treatment fidelity may explain the large and sustained effects in people with HF found in our trial. Further research is needed to evaluate CBT-I’s effectiveness and implementation strategies among people with HF in real-world clinical settings.
“Ultrasound Findings in Patients with Normal Nerve Conduction Despite Clinical Signs and Symptoms Consistent with Carpal Tunnel Syndrome.”
Authors: Chen Joseph , Fowler John R
Published: August 2022

Background:

Confirmatory methods such as nerve conduction studies (NCS) are often performed to support a clinical carpal tunnel syndrome diagnosis and to rule out other upper extremity pathologies. Ultrasonography (US) provides another diagnostic option, especially when NCS are discordant with history and physical examination. This study seeks to explore the correlation of US findings with clinical CTS diagnosis in patients with normal NCS.

Methods:

A database of 220 CTS patients was retrospectively analyzed to reveal 24 patients (28 hands) with clinically diagnosed CTS and normal NCS. Patient demographics and NCS and US findings were compared to those of a control group of non-CTS patients (42 patients, 52 hands). Median nerve cross-sectional area (CSA) was recorded, with values ≥ 10mm2 considered positive for CTS. Statistical and correlation analyses were performed between control and CTS groups comparing key parameters of interest.

Results:

Mean CSA was significantly increased in CTS patients with normal NCS than in controls. Similarly, the proportion of CTS positive, NCS negative patients with CSA measurements greater than 10mm2 was significantly greater than the proportion for control patients. Neither age nor BMI correlated with CSA measurements. NCS latencies and amplitudes did not correlate with ultrasound abnormalities.

Conclusions:

Clinically diagnosed CTS patients with normal NCS were found to have clinically significant median nerve CSA on ultrasound (10.1 ± 2.1 mm2, p<0.001). Furthermore, CSA measurements on ultrasound do not correlate with NCS parameters. These results suggest that ultrasound holds a unique diagnostic utility in the evaluation of CTS, especially when NCS are negative.
Early cleft lip repair: Demonstrating efficacy in the first 100 patients
Authors: Wlodarczyk Jordan R. , Wolfswinkel Erik M. , Liu Alice , Fahradyan Artur , Goel Pedram , Magee III William , Urata Mark M. , Hammoudeh Jeffrey A.
Published: August 2022

Background

Cleft lip and/or palate (CL/P) affect approximately 1/700 live births. Optimal timing for repair of cleft lip has yet to be objectively validated. Earlier repair takes advantage of a high degree of plasticity within the nasal cartilage and maxilla. We present patients enrolled in an early cleft lip repair (ECLR) protocol facilitating effective repair of the cleft lip and nostril.

Methods

ASA class I/II patients with unilateral cleft lip and/or palate undergoing repair < 3 months of age were enrolled over 5 years. Perioperative data, surgical and anesthetic complications, preoperative and postoperative nostril breadth (NB), nostril width (NW), nasal angle (NA), lip length (LL), frontal nasal breadth (FNB), and commissure length (CL) measured as ratios between cleft and non-cleft sides were abstracted. ECLR and Nasoalveolar molding (NAM) patients were matched for cleft lip severity using the cleft width ratios (CWR) and compared.

Results

The surgical and anesthetic complication rate for 100 ECLR patients was 2%. Operative and anesthetic times were 123 minutes (SD 37) and 177 minutes (SD 34), respectively. Hospital length of stay was 1 day (SD 0). Age at repair between ECLR and NAM was 33 days (SD 15) and 118 days (SD 33), respectively. After ECLR, preoperative to postoperative distance from symmetry for all anthropomorphic measurements improved (p < 0.001). Comparing severity matched ECLR to NAM patients, similar improvements were observed suggesting equivalent results (p > 0.05).

Conclusions

ECLR provides an efficacious method for correcting the cleft lip and nasal deformity that simulates NAM.
“Needle Aponeurotomy for Stage IV Dupuytren’s Contracture: A Wide-Awake First Step Approach in consecutive 204 rays.”
Authors: Denkler Keith A , Park Keon Min
Published: August 2022

Severe forms of Dupuytren’s disease (DD) are difficult to treat and surgical fasciectomy is often the first choice even with its high complication rate. At times, amputation is recommended. The objective of our study was to evaluate the efficacy of minimally invasive needle fasciotomy (needle aponeurotomy or NA) as the first and only treatment for severely (Stage IV) Dupuytren’s contracture by performing a retrospective chart review of a single surgeon’s consecutive experience over 8 years. 204 rays in 165 patients with severe DD with total passive extension digit contracture (TPED) with ≥135° were included in the study.

Mean follow up length was 22.3 months. Standard goniometric measurements of finger joint contractures were taken before NA and at follow up visits. There was a significant improvement in TPED as well as flexion contracture at each finger joint. Pre-procedure median flexion contractures were -70° (IQR -80 to -55) at MCPJ, -75° (IQR -85 to -65) at PIPJ, and -5° (-20 to 0) at DIPJ with the median TPED of -145° (IQR -160 to -135). Post-procedure flexion contractures improved with 74% gain at MCPJ, 32% gain at PIPJ, and 46% gain at DIPJ with overall 55% gain of TPED (p<0.001). Our study shows that NA led to significant improvements in joint contractures at all finger joints with minimal adverse effects. We believe NA is an effective and safe first-line treatment for severe DD as the sole treatment or preliminary step for more invasive procedures if needed.
Can the Immediate Implantation With Immediate Loading Achieve an Acceptable Esthetic Outcome? A Prospective Observational Clinical Study
Authors: Naeem Dalya M. , Al-Jumaily Hassanien A.
Published: August 2022

The trending protocol in implantology aims at integrating the esthetic on par with function while reducing discomfort and treatment time with optimal results. The purpose of this study was to evaluate the pink esthetic score in sites treated by graftless instant implantation that was boosted by instant provisionalization with a 2 to 3 mm jumping distance. Thirty-five implants were inserted in the extraction sockets of teeth of 29 healthy qualified patients (22 females and 7 males) with an age range of 23 to 60 years [mean±SD age 41.11±9.9 y). Preoperative assessment was complemented clinically and radiographically for each patient. The used system was Medentika dental implant (Germany). Osstell implant stability quotient was used to measure implant stability at the time of surgery (baseline) and at 16 weeks. Four implants in 3 patients failed. The implant survival rate was 88.6%. The protocol of this study produced a significant decrease in the jumping distance which is 2 to 3 mm at cone-beam computed tomography evaluation with satisfactory esthetic outcomes clinically. Further comparative studies with long-term and larger samples are needed to confirm the conclusion of this study.
The Application of Subcutaneous Radiofrequency After Liposuction for the Lower Face and Neck Contouring Under Local Anesthesia
Authors: Zhu Jingjing , Liu Tianyi , Zhou Yiqun , Guo Yu , Chen Liang
Published: August 2022

Background:

Radiofrequency-assisted liposuction (RFAL) is a new choice in energy-assisted body-contouring techniques. The purpose of this study is to observe the clinical effect and safety of RFAL on lower face and neck contouring under local anesthesia, and different outcome compared with traditional liposuction.

Methods:

From November 2016 to November 2020, a total of 72 patients with fat accumulation and skin laxity in lower face and neck, including 42 patients underwent subcutaneous radiofrequency after liposuction (group A) and 30 patients underwent traditional liposuction only (group B). The patient’s parameters recorded involved age, sex, body mass index, the volume of fat aspirated, energy delivered, operative time, and complications. They were photographed for comparison before and after treatment. At 3 and 6 months after the operation, improvement in skin tightening and patient satisfaction was surveyed postoperatively and assessed by third-party surgeons.

Results:

At 6 months after the operation, evaluations scores of the contouring outcome had significant difference between 2 groups (3.0±0.9 versus 2.5±1.0, P=0.045). There was no significant difference at 3 months (2.8±1.0 versus 2.6±1.0, P=0.265). Although the satisfaction rate of group A was higher than that of group B both at 3 months (76.2% versus 66.7%) and 6 months (80.9% versus 60.0%), there were no significant differences in average score (P>0.05). No significant complications or adverse events requiring further medical or surgical intervention after treatment.

Conclusion:

Subcutaneous radiofrequency after Liposuction is a safe and effective treatment that can achieve significant improvement of the fat accumulation and skin laxity of the lower face and neck under local anesthesia.
Videofluoroscopy Versus Nasopharyngoscopy of Lateral Pharyngeal Wall Movement for Assessment of Velopharyngeal Insufficiency
Authors: Sullivan Stephen R. , Taylor Helena O.B. , Stiles Emily , Nuss Roger C. , Balkin Daniel M. , Mulliken John B.
Published: August 2022

Background:

Competent speech requires closure of the velopharyngeal sphincter by dynamic apposition of the velum and posterior and lateral pharyngeal walls. An accurate estimation of lateral pharyngeal wall motion is an important determinant in the planning and the outcome of any operation to correct velopharyngeal insufficiency (VPI). The purpose was to compare the assessment of lateral pharyngeal wall movement by videofluoroscopy (VP) versus nasopharyngoscopy (NP).

Methods:

The authors retrospectively reviewed the charts of 269 consecutive patients in our cleft lip/palate clinic from 1982 to 2008 and culled those treated with a pharyngeal flap for VPI. The authors included patients who were evaluated preoperatively by both VP and NP, and had studies of suitable quality. Percentage of lateral pharyngeal wall motion was estimated with each technique and compared for each patient.

Results:

The authors identified 25 patients who underwent both VP and NP at the same median age (4.7 years). The estimated percentage of lateral pharyngeal wall motion between the 2 techniques was significantly different (P<0.001). Average lateral pharyngeal wall motion was estimated to be 59±25% (range: 5%–90%) by VP and only 40%±25% (range: 0%–95%) during NP.

Conclusions:

VP and NP are complementary, but assessment of lateral pharyngeal wall motion can vary between the 2 methods. The surgeon should be aware of the difference in estimated lateral pharyngeal wall movement when planning a procedure to correct VPI.
Complications of Diced Cartilage Wrapped in Blood Products in Rhinoplasty: A Meta-Analysis
Authors: Song Zhen , Dong Wenfang , Fan Fei
Published: August 2022

Background:

Diced cartilage wrapped in blood products has been increasingly advocated in rhinoplasty. The complication is a major concern of the procedure. This meta-analysis aims to assess the complication rates and revision rate of this procedure.

Methods:

All original articles published up to March 2022 were searched through PubMed, Embase, and Web of Science databases. Additional articles were added through reference searching. Articles were included for meta-analysis according to inclusion criteria. Data were extracted by 2 individuals independently and the analysis was conducted through Stata 12.0 software (StataCorp., College Station, Texas).

Results:

A total of 559 articles were initially found and an additional 1 article was added through reference searching. A total of 11 articles including 469 patients were included for meta-analysis. The results indicated that the total complication rates were 1.2% for irregularity, 0.2% for visibility, 0.7% for deviation, 1% for erythema, and 0% for graft resorption, depression, and infection. The revision rate was 1.2%.

Conclusions:

The overall complication and revision rates of diced cartilage wrapped in blood products in rhinoplasty were relatively low. Considering the limited number of related studies, a larger sample size, long-term follow-up, clear diagnostic criteria, and detailed methods of measurement are expected in further research.
Clostridium gelidum sp. nov., a psychrotrophic anaerobic bacterium isolated from rice field soil
Authors: Honma Sachi , Ueki Atsuko , Tonouchi Akio , Kaku Nobuo , Ueki Katsuji
Published: August 2022

A cold-adapted or psychrotrophic anaerobic bacterial strain (C5S11T) was isolated from rice field soil in Japan using an enrichment culture incubated at 5 °C. C5S11T grew at 0 °C and optimum growth was observed at 10 °C. Cells of C5S11T were Gram-stain-positive, motile, spore-forming rods with peritrichous flagella. C5S11T was assigned to a large branch consisted of various mesophilic species of the genus

Clostridium

in the phylogenetic trees reconstructed using the 16S rRNA gene sequences. The most closely related species of the strain was

Clostridium chromiireducens

DSM 23318T (98.5 % sequence similarity). C5S11T fermented various carbohydrates, including polysaccharides (starch, inulin, pectin and xylan), and produced acetate, butyrate and H2 as major products. The major cellular fatty acids were C16 : 0, C16 : 1ω9c, C14 : 0 and C16 : 1ω7c. The diagnostic diamino acid of the cell wall peptidoglycan was meso-diaminopimelic acid. The genome size of C5S11T was 6.04 Mb and the genomic DNA G+C content was 29.0 mol%. Average nucleotide identity by blast (ANIb), avaerage amino acid identity (AAI) and digital DNA–DNA hybridization (dDDH) values between the genomes of C5S11T and

C. chromiireducens

DSM 23318T were 80.0, 75.2 and 26.4 %, respectively. C5S11T had a gene encoding cold shock protein (RNA chaperone) in the genome, homologues of which have been found in psychrophilic species of the genus

Clostridium

. On the basis of the differences in the phylogenetic, genomic and phenotypic characteristics of C5S11T from those of the closely related species, a novel species, Clostridium gelidum sp. nov., is proposed to accommodate the strain. The type strain is C5S11T (=NBRC 114689T = DSM 112608T).
Participation in the nation-wide cervical cancer screening programme in Denmark during the COVID-19 pandemic: An observational study
Authors: Olesen Tina Bech , Jensen Henry , Møller Henrik , Jensen Jens Winther , Waldstrøm Marianne , Andersen Berit
Published: August 2022

Background

In contrast to most of the world, the cervical cancer screening programme continued in Denmark throughout the COVID-19 pandemic. We examined the cervical cancer screening participation during the pandemic in Denmark.

Methods

We included all women aged 23-64 years old invited to participate in cervical cancer screening from 2015-2021 as registered in the Cervical Cancer Screening Database combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of cervical cancer screening participation within 90, 180 and 365 days since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.

Results

Altogether, 2,220,000 invited women (in 1,466,353 individuals) were included in the study. Before the pandemic, 36% of invited women participated in screening within 90 days, 54% participated within 180 days and 65% participated within 365 days. At the start of the pandemic, participation in cervical cancer screening within 90 days was lower (pre-lockdown PR=0.58; 95% CI: 0.56-0.59 and 1st lockdown PR=0.76; 95% CI: 0.75-0.77) compared with the previous years. A reduction in participation within 180 days was also seen during pre-lockdown (PR=0.89; 95% CI: 0.88-0.90) and 1st lockdown (PR=0.92; 95% CI: 0.91-0.93). Allowing for 365 days to participation, only a slight reduction (3%) in participation was seen with slightly lower participation in some groups (immigrants, low education and low income).

Conclusions

The overall participation in cervical cancer screening was reduced during the early phase of the pandemic. However, the decline almost diminished with longer follow-up time.

Funding

The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.
ISCB RSG-Spain and highlights from the VIII Spanish Student Symposium in Bioinformatics and Computational Biology in 2021
Authors: Rivero Inés , Gorines-Cordero Guillermo Jorge , Rubio-Rodríguez Luis A. , Soler-Sáez Irene , Perpiñá-Clérigues Carla , García Adrian , Monzón Sara , Hernández-Beeftink Tamara
Published: August 2022

The Regional Student Group of Spain is recognized by the Student Council and the International Society for Computational Biology. The objective of these institutions is to connect and share useful information among all professionals and students working in the field of bioinformatics and computational biology. In this article, we intend to present and publicize RSG-Spain, the Spanish ISCB regional student group, by relating its recent history of a growing community of students and young professionals and how it helps their development in the field. RSG-Spain, since its creation, has been involved in the organization of events with the aim of gathering bioinformaticians in the country and promoting research and collaboration in the field. Here the VIII Student Symposium held online in 2021 is presented, analyzing the output of the event and showing the main challenges found in its organization.
Is adiposity associated with white-matter microstructural health and intelligence differently in men and women?
Authors: Patel Arjun , Chad Jordan A. , Chen J. Jean
Published: August 2022

The role of vascular risk in age-related brain degeneration has long been the subject of intense study. As a sub-category of vascular risk, obesity has an increasingly recognized role in influencing brain health and health-care strategies, but its association with brain health remains under-studied. Notably, no prior study has addressed sex differences in the association between adiposity and white-matter microstructural integrity, an important early marker of brain degeneration, despite known sex differences in fat storage and usage. This study focuses on the associations between adiposity (abdominal fat ratio: AFR, and liver proton density fat fraction: PDFF) and brain microstructural health (measures of white-matter microstructure using diffusion-tensor imaging, DTI). We found that fluid intelligence and reaction time are indeed associated with body fat differently in men and women. We also found significant differences in the associations of AFR with DTI metrics between sexes. These sex differences are mirrored in the associations of SBP and age with DTI metrics. Moreover, these sex differences in the AFR and SBP associations with DTI metrics persist when controlling for age. Taken together, these findings suggest that there are inherent sex-driven differences in how brain health is associated with vascular risk factors such as obesity.
Rates of COVID-19-Associated Hospitalization in Immunocompromised Individuals in Omicron-era: A Population-Based Observational Study Using Surveillance Data in British Columbia, Canada
Authors: Bahremand Taraneh , Yao Jiayun Angela , Mill Christopher , Piszczek Jolanta , Grant Jennifer M. , Smolina Kate
Published: August 2022

Background

People with immune dysfunction have a higher risk for severe COVID-19 outcomes. Omicron variant is associated with a lower rate of hospitalization but higher vaccine escape. This population-based study quantifies COVID-19 hospitalization rate in the Omicron-dominant era among vaccinated people with immune dysfunction, identified as clinically extremely vulnerable (CEV) population before COVID-19 treatment was widely offered.

Methods

All COVID-19 cases were reported to the British Columbia Centre for Disease Control (BCCDC) between January 7, 2022 and March 14, 2022. Case and population hospitalization rates were estimated across CEV status, age groups and vaccination status. Cumulative rates of hospitalizations for the study period were also compared between CEV and non-CEV individuals matched by sex, age group, region, and vaccination characteristics.

Findings

A total of 5,591 COVID-19 reported cases and 1,153 hospitalizations among CEV individuals were included. A third vaccine dose with mRNA vaccine offered additional protection against severe illness in CEV individuals. Vaccinated CEV population still had a significantly higher breakthrough hospitalization rate compared with non-CEV individuals.

Interpretation

CEV population remains a higher risk group and may benefit from additional booster doses and pharmacotherapy.

Funding

BC Centre for Disease Control and Provincial Health Services Authority
The role of epidemic spreading in seizure dynamics and epilepsy surgery
Authors: Millán Ana. P. , van Straaten Elisabeth C.W. , Stam Cornelis J. , Nissen Ida A. , Idema Sander , Baayen Johannes C. , Van Mieghem Piet , Hillebrand Arjan
Published: August 2022

Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but one in three patients continue to have seizures one year after surgery. In order to improve the chances of good outcomes, computational models of seizure dynamics are being integrated into surgical planning to simulate the effects of the planned surgeries. These modelling frameworks require several conceptual and methodological choices, as well as large amounts of patient-specific data, which hinders their clinical applicability. To address this problem, we considered the patient-specific brain network, derived from magnetoencephalography (MEG) recordings, and a simple epidemic spreading model as the dynamical basis for seizure propagation. This simple model was enough to reproduce the seizure propagation patterns derived from stereo-tactical electroencephalography recordings (SEEG) of all considered patients (N= 15), when the patients’ resected areas (RA) were used as the origin of epidemic spreading. The model yielded a more accurate fit for the seizure-free (SF,N= 11) than the non-SF (NSF) group and, even though the difference between the groups was not significant, the goodness-of-fit distinguished NSF from SF patients with an area under the curve AUC = 84.1%. We also explored the definition of a population model that combined data from different patients to fit the model parameters but was still individualized by considering the patient-specific MEG network. Even though the goodness-of-fit decreased compared to the individualized models, the difference between the SF and NSF groups held, and in fact became stronger and significant (p= 0.023), and the group classification also improved slightly (AUC= 88.6%). Therefore, combining data from different patients may pave the way not only to generalize this framework to patients without SEEG recordings, but also to reduce the risk of over-fitting and improve the stability of the models. Finally, we considered the individualized models to derive alternative hypothesis of the seizure onset zones and to test the surgical strategyin silicofor each patient. We found that RA regions were on average more likely to originate the seizures, but that alternative explanations were possible. Virtual resections of the RA when considering these alternative seeds significantly reduced seizure propagation, and to a greater extend for SF than NSF patients (although the difference was not significant). Overall, our findings indicate that spreading models based on the patient-specific MEG network can be used to predict surgical outcomes, with better fit results and greater reduction on seizure spreading linked to higher likelihood of seizure freedom after surgery.
Genetically-Encoded Discovery of Perfluoroaryl-Macrocycles that Bind to Albumin and Exhibit Extended Circulationin-vivo
Authors: Wong Jeffrey Y.K. , Kirberger Steven E. , Qiu Ryan , Ekanayake Arunika I. , Kelich Payam , Sarkar Susmita , Alvizo-Paez Edgar R. , Miao Jiayuan , Kalhor-Monfared Shiva , Dwyer John J. , Nuss John M. , Lin Yu-Shan , Macauley Matthew S. , Vukovic Lela , Pomerantz William C.K. , Derda Ratmir
Published: August 2022

In this paper, we report selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine SNAr chemistry. Modification of phage-displayed libraries SXCXnC-phage,n=3–5, where X is any amino acid except for cysteine by decafluoro-diphenylsulfone (DFS), yields genetically-encoded library of octafluoro-diphen-ylsulfone-crosslinked macrocycles (OFS-SXCXnC-phage). Selection from these libraries using albumin as a bait identified a family of significantly enriched perfluoroaryl-macrocycles. Synthesis of perfluoroaryl-macrocycles predicted by phage display and testing their binding properties by19F NMR and fluorescent polarization identifiedOFS-macrocycle with SICRFFC sequence as the most potent albumin binder. We observed thatOFS-macrocycles slowly react with biological nucleophiles such as glutathione. Replacing decafluoro-diphenylsulfone by nearly isosteric pentafluorophenyl sulfide yielded perfluorophenylsulfide (PFS)-crosslinked macrocycles devoid of undesired reactivity. The augmented leadPFS-macrocycle with SICRFFC sequence exhibitedKD= 4–6 μM towards human serum albumin and similar affinities towards rat and mouse albumins. When injected in mouse, thePFS-SICRFFCGGG compound was significantly retained in circulationin vivowhen compared to controlPFS-macrocyclic peptide. The perfluoroaryl-macrocycles with SICRFFC motif are the smallest known peptide macrocycle with significant affinity for human albumin and they are a productive starting point for future development of compact macrocycles with predictable circulation half-lifein vivo.
Determining predictive metabolomic biomarkers of meniscal injury in dogs with cranial cruciate ligament disease
Authors: Pye Christine R. , Green Daniel C. , Anderson James R. , Phelan Marie M. , Comerford Eithne J. , Peffers Mandy J.
Published: August 2022

Objectives

The objective of this study was to use for the first time proton nuclear magnetic resonance spectroscopy (1H NMR) to examine the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries. We hypothesised this would identify biomarkers of meniscal injury.

Methods

Stifle joint synovial fluid was collected from dogs undergoing stifle joint surgery or arthrocentesis for lameness investigations at three veterinary hospitals in the North-West of England. Samples underwent1H NMR spectroscopy and metabolite identification. We used multivariate and univariate statistical analysis to identify differences in the metabolomic profile between dogs with cranial cruciate ligament rupture and meniscal injury, cranial cruciate ligament rupture without meniscal injury, and neither cranial cruciate ligament rupture nor meniscal injury, taking into consideration specific clinical variables.

Results

154 samples of canine synovial fluid were included in the study. 64 metabolites were annotated to the1H NMR spectra. Six spectral regions were found to be significantly altered between groups with cranial cruciate ligament rupture with and without meniscal injury, including three attributed to NMR mobile lipids (mobile lipid -CH3[p=0.016], mobile lipid -n(CH3)3[p=0.017], mobile unsaturated lipid [p=0.031]).

Clinical Significance

We identified an increase in NMR mobile lipids in the synovial fluid of dogs with meniscal injury which are of interest as potential biomarkers of meniscal injury, as well as understanding the metabolic processes that occur with meniscal injury.
Fast and Accurate Kinship Estimation Using Sparse SNPs in Relatively Large Database Searches
Authors: Snedecor June , Fennell Tim , Stadick Seth , Homer Nils , Antunes Joana , Stephens Kathryn , Holt Cydne
Published: August 2022

1.

Forensic genetic genealogy (FGG) has primarily relied upon dense single nucleotide polymorphism (SNP) profiles from forensic samples or unidentified human remains queried against online genealogy database(s) of known profiles generated with SNP microarrays or from whole genome sequencing (WGS). In these queries, SNPs are compared to database samples by locating contiguous stretches of shared SNP alleles that allow for detection of genomic segments that are identical by descent (IBD) among biological relatives (kinship). This segment-based approach, while robust for detecting distant relationships, generally requires DNA quantity and/or quality that are sometimes not available in forensic casework samples. By focusing on SNPs with maximal discriminatory power and using an algorithm designed for a sparser SNP set than those from microarray typing, performance similar to segment matching was reached even in difficult casework samples. This algorithm locates shared segments using kinship coefficients in “windows” across the genome. The windowed kinship algorithm is a modification of the PC-AiR and PC-Relate tools for genetic relatedness inference, referred to here as the “whole genome kinship” approach, that control for the presence of unknown or unspecified population substructure. Simulated and empirical data in this study, using DNA profiles comprised of 10,230 SNPs (10K multiplex) targeted by the ForenSeq™ Kintelligence Kit demonstrate that the windowed kinship approach performs comparably to segment matching for identifying first, second and third degree relationships, reasonably well for fourth degree relationships, and with fewer false kinship associations. Selection criteria for the 10K SNP PCR-based multiplex and functionality of the windowed kinship algorithm are described.
A view of the pan-genome of domesticated cowpea (Vigna unguiculata[L.] Walp.)
Authors: Liang Qihua , Muñoz-Amatriaín María , Shu Shengqiang , Lo Sassoum , Wu Xinyi , Carlson Joseph W. , Davidson Patrick , Goodstein David M. , Phillips Jeremy , Janis Nadia M. , Lee Elaine J. , Liang Chenxi , Morrell Peter L. , Farmer Andrew D. , Xu Pei , Close Timothy J. , Lonardi Stefano
Published: August 2022

Cowpea,Vigna unguiculata L. Walp., is a diploid warm-season legume of critical importance as both food and fodder in sub-Saharan Africa. This species is also grown in Northern Africa, Europe, Latin America, North America, and East to Southeast Asia. To capture the genomic diversity of domesticates of this important legume,de novogenome assemblies were produced for representatives of six sub-populations of cultivated cowpea identified previously from genotyping of several hundred diverse accessions. In the most complete assembly (IT97K-499-35), 26,026 core and 4,963 noncore genes were identified, with 35,436 pan genes when considering all seven accessions. GO-terms associated with response to stress and defense response were highly enriched among the noncore genes, while core genes were enriched in terms related to transcription factor activity, and transport and metabolic processes. Over 5 million SNPs relative to each assembly and over 40 structural variants >1 Mb in size were identified by comparing genomes. Vu10 was the chromosome with the highest frequency of SNPs, and Vu04 had the most structural variants. Noncore genes harbor a larger proportion of potentially disruptive variants than core genes, including missense, stop gain, and frameshift mutations; this suggests that noncore genes substantially contribute to diversity within domesticated cowpea.

Article Summary

This study reports annotated genome assemblies of six cowpea accessions. Together with the previously reported annotated genome of IT97K-499-35, these constitute a pan-genome resource representing six subpopulations of domesticated cowpea. Annotations include genes, variant calls for SNPs and short indels, larger presence or absence variants, and inversions. Noncore genes are enriched for loci involved in stress response and harbor many genic variants with potential effects on coding sequence.
Frataxin deficiency disrupts mitochondrial respiration and pulmonary endothelial cell function
Authors: Culley Miranda K. , Mehta Monica , Zhao Jingsi , Perk Dror , Tai Yi Yin , Tang Ying , Shiva Sruti , Rabinovitch Marlene , Gu Mingxia , Bertero Thomas , Chan Stephen Y.
Published: August 2022

Deficiency of iron-sulfur (Fe-S) clusters promotes metabolic rewiring of the endothelium and the development of pulmonary hypertension (PH) in vivo. Joining a growing number of Fe-S biogenesis proteins critical to pulmonary endothelial function, recent data highlighted that frataxin (FXN) reduction drives Fe-S-dependent genotoxic stress and senescence across multiple types of pulmonary vascular disease. Trinucleotide repeat mutations in the FXN gene cause Friedreich’s ataxia, a disease characterized by cardiomyopathy and neurodegeneration. These tissue-specific phenotypes have historically been attributed to mitochondrial reprogramming and oxidative stress. Whether FXN coordinates both nuclear and mitochondrial processes in the endothelium is unknown. Here, we aim to identify the mitochondria-specific effects of FXN deficiency in the endothelium that predispose to pulmonary hypertension. Our data highlight an Fe-S-driven metabolic shift separate from previously described replication stress whereby FXN knockdown diminished mitochondrial respiration and increased glycolysis and oxidative species production. In turn, FXN-deficient endothelial cells exhibited a vasoconstrictive phenotype consistent with PH. These data were observed in both primary pulmonary endothelial cells after pharmacologic inhibition of FXN and inducible pluripotent stem cell-derived endothelial cells from patients with FXN mutations. Altogether, this study defines FXN as a shared upstream driver of pathologic aberrations in both metabolism and genomic stability. Moreover, our study highlights FXN-specific vasoconstriction, suggesting available and future therapies may be beneficial and targeted for PH subtypes with FXN deficiency.

Graphical Abstract
Reproductive state switches the valence of male urinary pheromones in female mice
Authors: Miller Caitlin H. , Reichard Tess M. , Yang Jay , Carlson-Clarke Brandon , Vogt Caleb C. , Warden Melissa R. , Sheehan Michael J.
Published: August 2022

Internal states shape responses to sensory stimuli. Mammalian female reproductive states are understudied considering they are one of the most regular state changes in the animal kingdom. Here we examine female house mouse preferences toward male odors across the reproductive states of estrus and late-stage pregnancy. In house mice, urine scent marks are salient social odors that convey information about the sex and identity of individuals by major urinary proteins (MUPs). Males secrete a sex-specific pheromonal protein called darcin (MUP20). Additionally, genetically diverse mice secrete unique combinations of MUPs used in individual recognition. Prior work has revealed that male odors are powerful social stimuli for female mice, yet we have a limited understanding of how the valence of such odors change across reproductive states. We discovered a valence shift among estrus and pregnant females toward novel male urine, in which estrus females exhibit preference and pregnant females show strong avoidance. This valence switch also occurs toward darcin alone, providing further support for darcin as a strong sexual signal. However, when presented with familiar male urine, the approach-avoidance response disappears, even when additional darcin is added. In contrast, when an existing identity protein (MUP11) is added to familiar male urine the approach-avoidance response is recovered. This indicates that darcin in the absence of other identity information denotes a novel male and that familiar identity information present in male urine is sufficient to modify responses to darcin. Our findings suggest that the sex and identity information encoded by MUPs are likely processed via distinct, and potentially opposing pathways, that modulate responses toward complex social odor blends. Furthermore, we identify a state-modulated shift in decision-making toward social odors and propose a neural circuit model for this flow of information. These data underscore the importance of physiological state and signal context for interpreting the meaning and importance of social odors.
Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function
Authors: Molendijk Jeffrey , Blazev Ronnie , Mills Richard J. , Ng Yaan-Kit , Watt Kevin I. , Chau Daryn , Gregorevic Paul , Crouch Peter J. , Hilton James B.W. , Lisowski Leszek , Zhang Peixiang , Reue Karen , Lusis Aldons J. , Hudson James E. , James David E. , Seldin Marcus M. , Parker Benjamin L.
Published: August 2022

Improving muscle function has great potential to improve the quality of life. To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis. These data identified thousands of associations between protein abundance and phenotypes and can be accessed online (https://muscle.coffeeprot.com/) to identify regulators of muscle function. We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle. This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show UFMylation is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.
A machine learning model for disease risk prediction by integrating genetic and non-genetic factors
Authors: Xu Yu , Wang Chonghao , Li Zeming , Cai Yunpeng , Young Ouzhou , Lyu Aiping , Zhang Lu
Published: August 2022

Polygenic risk score (PRS) has been widely used to identify the high-risk individuals from the general population, which would be helpful for disease prevention and early treatment. Many methods have been developed to calculate PRS by weighted aggregating the phenotype-associated risk alleles from genome-wide association studies. However, only considering genetic effects may not be sufficient for risk prediction because the disease risk is not only related to genetic factors but also non-genetic factors, e.g., diet, physical exercise et al. But it is still a challenge to integrate these genetic and non-genetic factors into a unified machine learning framework for disease risk prediction. In this paper, we proposed PRSIMD (PRS Integrating Multi-source Data), a machine learning model that applies posterior regularization to integrate genetic and non-genetic factors to improve disease risk prediction. Also, we applied Mendelian Randomization analysis to identify the causal non-genetic risk factors for the selected diseases. We applied PRSIMD to predict type 2 diabetes and coronary artery disease from UK Biobank and observed that PRSIMD was significantly better than the methods to calculate PRS including p-value threshold (P+T), PRSice2, SBLUP, DMSLMM, and LDpred2. In addition, we observed that PRSIMD achieved the better predictive power than the composite risk score.
In vivo suppression of polyglutamine aggregation via co-condensation of the molecular chaperone DNAJB6
Authors: de Mattos Eduardo Preusser , Musskopf Maiara Kolbe , Bergink Steven , Kampinga Harm H.
Published: August 2022

Amyloidogenic protein aggregation is a hallmark of several human neurodegenerative conditions, including Alzheimer’s, Parkinson’s, and Huntington’s disease (HD). Mutations and/or environmental stresses trigger conformational transition of specific proteins to amyloids, conferring them with gain of toxic function, which eventually leads to cell death in distinct brain areas. Cumulative data indicate that modulation of specific molecular chaperones can alleviate many of the pathological features of protein aggregation diseases. We previously showed that the Hsp70 co-chaperone DNAJB6 is among the strongest suppressors of amyloid aggregation, and that moderate DNAJB6 overexpression significantly extents lifespan of a mouse model of aggressive HD pathology. DNAJB6 alone delays amyloidogenic aggregation in vitro by several orders of magnitude at substoichiometric ratios, but its activity in cells is less efficient, albeit still markedly superior to most known anti-amyloidogenic agents. This suggests that downstream PQC factors are necessary for full DNAJB6-mediated suppression of aggregation in vivo, which might have to be co-stimulated in therapeutic strategies targeting DNAJB6 action. We explored here the PQC pathways required for optimal DNAJB6 inhibition of polyglutamine (polyQ) aggregation, focusing on the two main cellular proteolytic machineries: proteasomes and macroautophagy. Unexpectedly, DNAJB6 activity was largely insensitive to chemical blockage of either degradative pathway. Instead, live cell imaging unveiled a co-condensation mechanism of DNAJB6 with mobile polyQ assemblies. DNAJB6 was not required for polyQ condensation, but its expression increased the percentage of cells with mobile condensates by a factor of 3, suggesting that DNAJB6 prevents polyQ condensates to convert from the soluble to the solid state. This in turn, may keep the polyQ peptides competent for (regulated) degradation and accessible to factors allowing its extraction from the condensed state.
Do markets react to corporate governance reforms? Evidence from a developing economy
Authors: Ndegwa James Ndirangu
Published: August 2022

Purpose

The purpose of this study is to investigate market reaction to corporate governance reform pronouncements on board diversity in Kenyan listed firms.

Design/methodology/approach

An event study was performed using 240 days pre-event period and an event period that consisted of 25 days pre and 25 days post the March 2016 board diversity reforms announcement in Kenya. The difference in differences (DiD) method was also used for cause–effect analysis for two years before and three years after the March 2016 board diversity reforms announcement. The outcome variable was firm value, whereas the treatment and control groups were Kenyan listed firms and deposit-taking credit unions, respectively.

Findings

The event study method found cumulative abnormal returns after the date of the board diversity reforms announcement to be positive and significant. The DiD methods found a positive and significant market reaction to the March 2016 board diversity reforms announcement in Kenya.

Research limitations/implications

This study was limited by the secondary data that was collected and analyzed from financial statements and stock price data from the Nairobi Securities Exchange (NSE). Financial statements have the disadvantage of being affected by the judgment and estimates of their preparers or accountants.

Practical implications

Emerging markets like the NSE are vulnerable to market manipulation by insiders. Efficient stock markets are known to attract more investors who are interested in a trustworthy stock price determination mechanism. The Capital Market Authority should thus continue implementing corporate governance reforms aimed at improving the efficiency of the NSE and the trustworthiness of stock prices therein. The continued reforms thus imply better value for money for the NSE investors.

Originality/value

This study makes an important contribution to literature by combining an event study and DiD analysis to assess market reaction to board diversity reform announcements in emerging markets of sub-Saharan Africa which is a concept that has not been researched before. Past studies have used event studies to investigate the efficiency status of stock markets in sub-Saharan Africa, whereas the current study used an additional method of DiD and hence contributed to literature.