bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of feeding mid- or zero-tannin faba bean cultivars differing in vicine and covicine content on diet nutrient digestibility and growth performance of weaned pigs
Authors: Nyende Protus W , Wang Li Fang , Zijlstra Ruurd T , Beltranena Eduardo
Published: April 2022

To prioritize what cultivars to grow to feed pigs, five faba bean cultivars including three zero-tannin, high vicine and covicine cultivars (Snowbird, Snowdrop, Tabasco), and two medium-tannin, lower vicine and covicine cultivars (Fabelle and Malik) were fed to compare effects on diet nutrient digestibility and growth performance of weaned pigs. A total of 260 pigs (8 ± 1.2 kg), weaned at 20 ± 1 d of age housed 2 barrows and 2 gilts/pen were fed 1 of 5 dietary regimens starting 1-week post-weaning for 4 weeks in a randomized complete block design. Diets including each cultivar at 20% or 30% provided 10.2 and 10.1 MJ net energy (NE)/kg and 1.3 and 1.2 g standardized ileal digestible (SID) lysine (Lys)/MJ NE in phases 1 and 2, respectively. Digestibility data were analyzed using PROC GLIMMIX and growth performance data were analyzed using PROC MIXED with pen as experimental unit. Fabelle contained the most condensed tannins (CT; 0.53%) but the least vicine (0.04%) and covicine (0.01%). Zero-tannin cultivars contained little CT (<0.2%) but had the greatest vicine (0.5%) and covicine content (0.4%). For phase 1, diet apparent total tract digestibility (ATTD) of dry mater (DM), gross energy (GE), crude protein (CP), digestible energy (DE), and NE values did not differ among cultivars. For phase 2, diet ATTD of DM and GE were greatest (P < 0.05) for Snowdrop and Tabasco, intermediate for Fabelle, and lowest for Malik; Snowbird was not different from Fabelle or Malik. Diet ATTD of CP was greatest (P < 0.05) for Tabasco, intermediate for Snowbird, and lowest for Malik; Snowdrop was not different from Tabasco or Snowbird, and Fabelle was not different from Snowbird or Malik. Diet DE and NE values were greatest (P < 0.05) for Tabasco, intermediate for Fabelle and Snowdrop, and lowest for Snowbird; Malik was not different from Fabelle or Snowbird. For the entire trial (d 0–28), daily feed disappearance and weight gain for pigs fed Fabelle were 10% greater (P < 0.05) than those fed Malik; pigs fed zero-tannin cultivar diets were intermediate. Pigs fed Fabelle were 1.6 kg heavier (P < 0.05) than those fed Malik at the end of the trial; pigs fed zero-tannin cultivar diets were intermediate. In conclusion, growth performance of pigs fed faba bean cultivar diets was more related to feed disappearance than diet nutrient digestibility. Vicine and covicine instead of condensed tannin content of faba bean cultivars seemed more relevant to growth performance in weaned pigs.
Using the Greater Tuberosity as a Reference for Placement of Proximal Humerus Plates Leads to a High Rate of Calcar Screw Malposition
Authors: Patel Midhat , Castaneda Paulo , Kisana Haroon , Roache William K. , Dehghan Niloofar , McKee Michael D. , Amini Michael H.
Published: April 2022

Objectives:

Achieving calcar fixation is critical to minimize the failure of proximal humerus fractures repaired with proximal humeral locking plates (PHLPs). Many operative technique manuals reference the greater tuberosity (GT) for plate placement. The objective of this study was to examine the accuracy of calcar screw placement when PHLPs were placed based on distance from the GT.

Methods:

Twenty cadaveric specimens were acquired representing a height distribution across the US population. Thirteen different PHLPs were applied. A drill bit was placed through the designated calcar screw hole and measured on radiographs, with the inferior 25% of the head representing an ideal placement.

Results:

Three hundred fifty constructs were studied. In 28% of the specimens, the calcar screw was misplaced. In 20% of the specimens, it was too low, whereas in 8%, it was too high. The calcar screw missed low in 30% of patients shorter than 5 feet, 5.5 inches versus 8% of taller patients (P= 0.007). It missed high in 13% of taller patients versus 2% of shorter patients (P= 0.056). Calcar screws in variable-angle plates missed 0% of the time, whereas those in fixed-angle plates missed 36% of the time (P= 0.003).

Conclusions:

Placement of PHLPs based on distance from the GT results in unacceptable position of the calcar screw 28% of the time and up to 36% in fixed-angle plates. This could be further compounded if the GT is malreduced. Current technique guide recommendations result in an unacceptably high rate of calcar screw malposition.
Immunogenicity Associated with Aesthetic Botulinumtoxin A: A Survey of Asia-Pacific Physicians’ Experiences and Recommendations
Authors: Park Je-Young , Corduff Niamh , Frevert Jürgen , Wanitphakdeedecha Rungsima , Chao Yates Y.Y.
Published: April 2022

Background:

Most botulinum toxin A (BoNT/A) products contain unnecessary bacterial components that increase the risk of developing neutralizing antibodies (nAbs). Reports of secondary nonresponse and treatment failures (STF) due to nAbs have accompanied a surge in new BoNT/A products.

Methods:

To formulate recommendations on managing toxin resistance, we reviewed the evidence on BoNT/A-associated immunogenicity and evaluated Asian physicians' current BoNT/A practices, knowledge, and real-world experiences, as provided by survey outcomes conducted with 128 Asian experts (regular botulinum toxin injectors).

Results:

Most doctors believe STF occurs, some patients exhibit partial symptoms, and impurities (eg, complexing proteins) in BoNT/A preparations risk STF. Bioassays that distinguish non-nAbs from nAbs that hinder toxin function remain unavailable to most doctors, though most would perform testing if given the option. Doctors in the Asia-Pacific region have differing strategies for managing STF, depending on the availability of alternatives or tests. They recommended switching to a highly-purified formulation free of complexing proteins and other impurities to lower the risk of immunogenicity, or offering treatment holidays of 2 -2.5 years. They suggested restarting treatment with the same highly purified formulation, especially for repeated treatments, large-dose injections, and younger patients who will accumulate higher lifetime doses, so as to minimize immunogenic risks and preserve long-term treatment outcomes. Importantly, doctors should always initiate patients on pure formulations rather than switching to these only after resistance develops.

Conclusion:

Choosing highly purified BoNT/A products at treatment initiation enhances long-term efficacy and patient satisfaction while minimizing the risk of immune activation and nAb formation.
Early Expression of MMP-9 Predicts Recovery of Tibialis Anterior after Sciatic Nerve Crush Injury
Authors: Brogan David M. , Dy Christopher J. , Wever Jason , Lee Tony , Achilefu Samuel
Published: April 2022

Background:

The purpose of this study was to assess the expression of molecular markers and epineural blood flow after differing degrees of nerve injury to identify potential tools to predict nerve recovery in a rat sciatic nerve model.

Methods:

A total of 72 rats were divided into nine groups. Each group was subjected to one of three crush injuries, created by applying one of three vascular clamps for 30 seconds. Vascularity was assessed with laser Doppler flowmetry before and after crush, and at nonsurvival surgery. Nonsurvival surgeries were performed 6 hours, 2 weeks, or 6 weeks later with nerve conduction studies and muscle strength testing. Expression of matrix metalloproteinase 9 (MMP-9) and matrix metalloproteinase 2 (MMP-2) in each nerve was quantified using with enzyme linked immunosorbent analysis.

Results:

Persistent hyperemia was noted in the zone of injury compared with baseline at 2 weeks and 6 weeks in the groups that displayed incomplete recovery. Expression of MMP-9 at 6 hours increased with increasing severity of crush and was inversely related to tibialis anterior muscle force recovery. The ratio of MMP-9:MMP-2 expression correlated well with recovery of compound nerve action potential amplitude at 6 weeks.

Conclusions:

Resolution of nerve hyperemia may correlate with nerve recovery from trauma, but early measures of nerve blood flow after injury are not prognostic of recovery. Ratio of MMP-9:MMP-2 expression 6 hours after injury correlates with recovery of compound nerve action potential at 6 weeks, while MMP-9 expression alone predicts tibialis anterior recovery. These findings together suggest that increased MMP-9 expression is a potentially useful marker of more severe nerve injury.
Current Trends in Breast Reconstruction following Bilateral Prophylactic Mastectomy
Authors: Hu Vivian J. , McCleary Sean P. , Smullin Carolyn P. , Rosales Morales Ricardo , Da Lio Andrew L.
Published: April 2022

Background:

Individuals with genetic susceptibility to breast cancer may pursue bilateral prophylactic mastectomy (BPM) and subsequent breast reconstruction. This study aimed to characterize immediate reconstructive trends following BPM.

Methods:

The ACS-NSQIP database (2010 -2019) was used to examine differences in demographics and operative outcomes based on breast reconstruction technique following BPM and factors predicting reconstruction type.

Results:

Of 1945 patients (mean age, 43.8 ± 11.3 years), implant-based reconstruction (IBR) was most frequently (71.8%) performed following BPM. Patients who underwent IBR (n = 1396) were younger (42.6 years, P < 0.001), more likely to be White (P < 0.05), and more likely to have a BMI less than 25 (P < 0.001). Patients who underwent autologous reconstruction (AR) (n = 186, 45.8 years) were more likely to be Black or African American and have a BMI of 25–30. Patients who underwent mastectomy only (MO) without immediate reconstruction (n = 363) were older (47.6 years), more likely to be Asian, and more likely to have a BMI greater than 35. The MO cohort had the highest frequency of diabetes or smoking history. AR was associated with longer operations, longer lengths of stay, and increased complications. Increasing age and BMI were predictive of AR or MO compared to IBR. Smoking was predictive of MO.

Conclusion:

This is the first large-scale study of genetically susceptible patients who underwent BPM demonstrating a significant relationship between patient demographics, operative outcomes, and immediate reconstruction technique. These results provide valuable insight for surgeons and patients during the shared decision-making process.
Adults' State of Using Complementary and Alternative Medicine During the COVID-19 Pandemic
Authors: Delibaş Leyla , Polat Filiz , Ekren Çakici Aynur
Published: April 2022

This study aimed to explore the attitudes of adults living in Turkey toward complementary and alternative medicine in the period of the coronavirus disease-2019 (COVID-19) pandemic and identify whether Turkish adults used complementary and alternative medicine during the pandemic. The cross-sectional study covered 3242 adults across Turkey. The data were collected via a Personal Information Form and the Holistic Complementary and Alternative Medicine Questionnaire. The participants had positive attitudes toward complementary and alternative medicine (33.8 ± 4.7). The results indicated that the Turkish adults widely used complementary and alternative treatment methods (70.5%) during the COVID-19 pandemic, and they were more oriented toward the use of herbal treatment (35.5%). It was identified that the primary reasons for using complementary and alternative medicine were to be protected from COVID-19, and if infected with COVID-19, to recover from it quickly with only mild symptoms.
Benson Relaxation Technique Combined With Music Therapy for Fatigue, Anxiety, and Depression in Hemodialysis Patients
Authors: Eroglu Hacer , Gok Metin Zehra
Published: April 2022

This study aimed to investigate the effects of the Benson relaxation technique combined with music therapy on fatigue, anxiety, and depression levels of patients undergoing hemodialysis. This randomized controlled study was conducted with 61 patients (30 patients in the intervention group, 31 patients in the control group) in a province located in Turkey. This 8-week, randomized, clinical trial was carried out in 2 hemodialysis units. After the patients in both groups were informed about the study, the Piper Fatigue Scale and the Hospital Anxiety and Depression Scale were administered to the patients. All subdomain scores of the Piper Fatigue Scale in the intervention group were significantly lower at weeks 4, 8, and 10 than those of the control group (P < .05). The intervention group had significantly lower Anxiety subscale scores than those of the control group at week 10 (P < .05). Similarly, Depression subscale scores were significantly lower in the intervention group at weeks 8 and 10 than those in the control group (P < .05). The findings suggest that Benson relaxation technique combined with music therapy is an effective approach to manage fatigue, anxiety, and depression symptoms related to hemodialysis.
The Impact of Maternal Syphilis and Associated Factors on HIV Vertical Transmission
Authors: Hoff Calegari Lisiane , Friedrich Luciana , Rech Astolfi Vitória , Kerber Juliana Maria , Andrades Gustavo Santos , Da Silva Clécio Homrich
Published: April 2022

Maternal syphilis may increase HIV vertical transmission or it may be a marker of other risk factors. In a Brazilian historical series, HIV vertical transmission risk was higher in newborns exposed to maternal syphilis-HIV co-infection than in newborns exposed to maternal HIV infection alone. Maternal syphilis was a risk factor for HIV vertical transmission independent of education and prenatal visits but not independent of maternal elevated HIV viral loads or inadequate maternal antiretroviral treatment.
Trends in Time to Extubation for Pediatric Postoperative Cardiac Patients and Its Correlation With Changes in Clinical Outcomes: A Virtual PICU Database Study*
Authors: Epstein Rebecca , Ohliger Shelley J. , Cheifetz Ira M. , Malay Sindhoosha , Shein Steven L.
Published: April 2022

OBJECTIVES:

Mechanical ventilation is often used in children after cardiac surgery but can impair hemodynamics and cause lung injury. Early extubation may improve ICU length of stay and survival. We aimed to describe trends in early extubation rates and evaluate if centers that more commonly practice early extubation have better severity-adjusted outcomes.

DESIGN:

Retrospective analysis was performed of admissions in the Virtual Pediatric Systems (VPS, LLC) database from 2009 to 2018. Early extubation was defined as patients extubated in the operating room or within 6 hours of PICU admission.

SETTING:

PICUs participating in the VPS database.

PATIENTS:

Children in the VPS database who underwent cardiac surgery.

INTERVENTIONS:

None.

MEASUREMENT AND MAIN RESULTS:

Among 69,739 subjects, 20% were neonates, 47% underwent early extubation, 5.3% failed extubation, and 2.5% died. Overall, early extubation rates did not change over the study period. Centers were placed in one of four groups based on their early extubation rate in lower complexity surgeries. Centers that most commonly used early extubation had more ICU-free time among all patients in univariable analysis (lowest early extubation group, 23.8 d [interquartile range, 18.2–25.9 d]; highest early extubation group, 24.7 d [20.0–26.2 d]; p < 0.001). After adjusting for center volume, sex, age, surgical complexity, and preoperative ICU admission, increasing center-level early extubation rates were not associated with more ICU-free days. Higher center-level early extubation rate was not associated with mortality in univariable or multivariable analysis but was associated with decreased extubation failure rate (lowest early extubation group, 6.4%; highest early extubation group, 3.6%; p < 0.001).

CONCLUSIONS:

In this large, multicenter database study, early extubation rates in postoperative cardiac patients did not significantly change between 2009 and 2018. Centers that performed early extubation more frequently did not have shorter ICU stays or difference in mortality rates but did have lower reintubation rates.
Impact of Predatory Journals in Plastic Surgery Literature: Researchers Beware
Authors: Asaad Malke , Elmorsi Rami , Winocour Sebastian , Mericli Alexander F. , Reece Edward , Selber Jesse C. , Butler Charles E. , Chu Carrie K.
Published: April 2022

Background:

Predatory journals have exploited the open access publishing model and are considered as a major threat to the integrity of scientific research. The goal of this study was to characterize predatory publishing practices in plastic surgery.

Methods:

To identify potentially predatory journals in the field of plastic surgery, the authors searched the Cabells’ Predatory Reports and Beall’s List using preidentified keywords. For presumed legitimate open access journals, the Directory of Open Access Journals (DOAJ) was queried. The characteristics of potentially predatory journals were compared to those of legitimate open access plastic surgery journals.

Results:

The authors identified a total of 25 plastic surgery–focused journals. Out of the 25 potentially predatory journals, only 15 journals had articles published within the last 5 years, with a mean number of articles of 33 ± 39 (range, 2 to 159 articles). The mean number of predatory violations according to Cabells’ criteria was 6.8 ± 1.4 (range, 3 to 9). Using the DOAJ database, the authors identified a total of 24 plastic surgery–related journals. Compared to potentially predatory journals, journals from the DOAJ were more likely to be indexed in PubMed (0 versus 50 percent, respectively, p < 0.0001). Time to publication was significantly higher in journals from the DOAJ (17 ± 7 versus 4 ± 1 weeks; p = 0.006). Despite higher article processing charges in the DOAJ group, this difference was not statically significant ($1425 ± $717 versus $1071 ± $1060; p = 0.13).

Conclusions:

Predatory journals are pervasive in the medical literature and plastic surgery is no exception. Plastic surgeons should practice due diligence when choosing a target journal for their articles. Journals with predatory practices should be distinguished from legitimate open access publication platforms.
Parenting in Plastic Surgery Residency
Authors: Wallace Chelsea C. , Edmunds R. Wesley , Bourne Debra , Wong Lesley
Published: April 2022

Background:

In 1994, Mackinnon advocated that plastic surgery residents should have accessible child care to promote a productive return to work. Decades later, lack of adequate child care remains a dilemma for trainees. The authors’ survey aims to evaluate childrearing during plastic surgery training.

Methods:

An anonymous, voluntary survey was sent to plastic surgery residents. It evaluated demographics, childcare accommodations, and attitudes/issues surrounding childrearing during residency.

Results:

There were 32 respondents: 66 percent women and 34 percent men. Seventy-five percent were married, and 38 percent were parents. Seventy-five percent of male parents compared to 12 percent of female parents reported that their spouse was the primary childcare source. One hundred percent of respondents with children reported that child care creates a financial burden. Three percent of respondents felt their institution provided services to arrange adequate child care. Sixty-three percent of residents felt their program did not allow flexibility to accommodate childcare needs. Female residents missed work twice as often and were twice as likely to require a co-resident to cover clinical duties because of childcare difficulties when compared to male residents (p = 0.296 and p = 0.145). Sixty-seven percent of women agreed with the statement, “If you had to pick a residency program today, the availability of on-site child care would influence your decision,” compared to only 9 percent of men (p = 0.002).

Conclusions:

Training institutions are not meeting the childcare needs of plastic surgery trainees. If the specialty wishes to recruit and retain the top applicants, it must improve the childcare accommodations for residents. All institutions with plastic surgery residency programs should provide affordable, accessible child care that accommodates the 24-hour natures of both patient care and parenthood.
The background and legacy of Lewontin's apportionment of human genetic diversity
Authors: Novembre John
Published: April 2022

Lewontin's 1972 article ‘The apportionment of human diversity’ described a key feature of human genetic diversity that would have profound impacts on conversations regarding genetics and race: the typical genetic locus varies much less between classical human race groupings than one might infer from inspecting the features historically used to define those races, like skin pigmentation. From this, Lewontin concluded: ‘Human racial classification … is now seen to be of virtually no genetic or taxonomic significance’ (p. 397). Here, 50 years after the paper's publication, the goal is to understand the origins and legacy of the paper. Aided by insights from published papers and interviews with several of Lewontin's contemporaries, I review the 1972 paper, asking about the intellectual background that led to the publication of the paper, the development of its impact, the critiques of the work and the work's application and limitations today. The hope is that by gaining a clearer understanding of the origin and reasoning of the paper, we might dispel various confusions about the result and sharpen an understanding of the enduring value and insight the result provides.

This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Human genetic admixture through the lens of population genomics
Authors: Gopalan Shyamalika , Smith Samuel Pattillo , Korunes Katharine , Hamid Iman , Ramachandran Sohini , Goldberg Amy
Published: April 2022

Over the past 50 years, geneticists have made great strides in understanding how our species' evolutionary history gave rise to current patterns of human genetic diversity classically summarized by Lewontin in his 1972 paper, ‘The Apportionment of Human Diversity’. One evolutionary process that requires special attention in both population genetics and statistical genetics is admixture: gene flow between two or more previously separated source populations to form a new admixed population. The admixture process introduces ancestry-based structure into patterns of genetic variation within and between populations, which in turn influences the inference of demographic histories, identification of genetic targets of selection and prediction of complex traits. In this review, we outline some challenges for admixture population genetics, including limitations of applying methods designed for populations without recent admixture to the study of admixed populations. We highlight recent studies and methodological advances that aim to overcome such challenges, leveraging genomic signatures of admixture that occurred in the past tens of generations to gain insights into human history, natural selection and complex trait architecture.

This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Mathematical constraints onFST: multiallelic markers in arbitrarily many populations
Authors: Alcala Nicolas , Rosenberg Noah A.
Published: April 2022

Interpretations of values of theFSTmeasure of genetic differentiation rely on an understanding of its mathematical constraints. Previously, it has been shown thatFSTvalues computed from a biallelic locus in a set of multiple populations andFSTvalues computed from a multiallelic locus in a pair of populations are mathematically constrained as a function of the frequency of the allele that is most frequent across populations. We generalize from these cases to report here the mathematical constraint onFSTgiven the frequencyMof the most frequent allele at amultialleliclocus in a set ofmultiplepopulations. Using coalescent simulations of an island model of migration with an infinitely-many-alleles mutation model, we argue that the joint distribution ofFSTandMhelps in disentangling the separate influences of mutation and migration onFST. Finally, we show that our results explain a puzzling pattern of microsatellite differentiation: the lowerFSTin an interspecific comparison between humans and chimpanzees than in the comparison of chimpanzee populations. We discuss the implications of our results for the use ofFST.

This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
How HLA diversity is apportioned: influence of selection and relevance to transplantation
Authors: Maróstica André Silva , Nunes Kelly , Castelli Erick C. , Silva Nayane S. B. , Weir Bruce S. , Goudet Jérôme , Meyer Diogo
Published: April 2022

In his 1972 paper ‘The apportionment of human diversity’, Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low
F
ST
values. However, when we analyse haplotypes defined by these SNPs (which define ‘HLA alleles’), we find marked differences in frequencies between geographic regions. These differences are not reflected in the
F
ST
values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting
F
ST
. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry.

This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Forensic genetics through the lens of Lewontin: population structure, ancestry and race
Authors: Jobling Mark A.
Published: April 2022

In his famous 1972 paper, Richard Lewontin used ‘classical’ protein-based markers to show that greater than 85% of human genetic diversity was contained within, rather than between, populations. At that time, these same markers also formed the basis of forensic technology aiming to identify individuals. This review describes the evolution of forensic genetic methods into DNA profiling, and how the field has accounted for the apportionment of genetic diversity in considering the weight of forensic evidence. When investigative databases fail to provide a match to a crime-scene profile, specific markers can be used to seek intelligence about a suspect: these include inferences on population of origin (biogeographic ancestry) and externally visible characteristics, chiefly pigmentation of skin, hair and eyes. In this endeavour, ancestry and phenotypic variation are closely entangled. The markers used show patterns of inter- and intrapopulation diversity that are very atypical compared to the genome as a whole, and reinforce an apparent link between ancestry and racial divergence that is not systematically present otherwise. Despite the legacy of Lewontin's result, therefore, in a major area in which genetics coincides with issues of public interest, methods tend to exaggerate human differences and could thereby contribute to the reification of biological race.

This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Changing patterns in reporting and sharing of review data in systematic reviews with meta-analysis of the effects of interventions: a meta-research study
Authors: Nguyen Phi-Yen , Kanukula Raju , McKenzie Joanne E , Alqaidoom Zainab , Brennan Sue E , Haddaway Neal R , Hamilton Daniel G , Karunananthan Sathya , McDonald Steve , Moher David , Nakagawa Shinichi , Nunan David , Tugwell Peter , Welch Vivian A , Page Matthew J
Published: April 2022

Objectives: To examine changes in completeness of reporting and frequency of sharing data, analytic code and other review materials in systematic reviews (SRs) over time; and factors associated with these changes. Design: Cross-sectional meta-research study. Sample: A random sample of 300 SRs with meta-analysis of aggregate data on the effects of a health, social, behavioural or educational intervention, which were indexed in PubMed, Science Citation Index, Social Sciences Citation Index, Scopus and Education Collection in November 2020. Analysis/Outcomes: The extent of complete reporting and frequency of sharing review materials in these reviews were compared with 110 SRs indexed in February 2014. Associations between completeness of reporting and various factors (e.g. self-reported use of reporting guidelines, journal's data sharing policies) were examined by calculating risk ratios (RR) and 95% confidence intervals (CI). Results: Several items were reported sub-optimally among 300 SRs from 2020, such as a registration record for the review (38%), a full search strategy for at least one database (71%), methods used to assess risk of bias (62%), methods used to prepare data for meta-analysis (34%), and funding source for the review (72%). Only a few items not already reported at a high frequency in 2014 were reported more frequently in 2020. There was no evidence that reviews using a reporting guideline were more completely reported than reviews not using a guideline. Reviews published in 2020 in journals that mandated either data sharing or inclusion of Data Availability Statements were more likely to share their review materials (e.g. data, code files) (18% vs 2%). Conclusion: Incomplete reporting of several recommended items for systematic reviews persists, even in reviews that claim to have followed a reporting guideline. Data sharing policies of journals potentially encourage sharing of review materials.
Tumor necrosis factor α modulates excitatory and inhibitory neurotransmission in a concentration-dependent manner
Authors: Kleidonas Dimitrios , Kirsch Matthias , Andrieux Geoffroy , Pfeifer Dietmar , Boerries Melanie , Vlachos Andreas
Published: April 2022

Microglia, the brain’s resident immune cells, have been implicated in important brain functions, such as synaptic transmission and plasticity. The pro-inflammatory cytokine tumor necrosis factor α (TNFα), which is produced and secreted by microglia, has been linked to the expression of synaptic plasticity in neurons. However, the role of TNFα-mediated activation of microglia has not been addressed in this context. Here, we assessed concentration-dependent effects of TNFα on the balance of synaptic excitation/inhibition and the activation of microglia using mouse organotypic entorhino-hippocampal tissue cultures. We found that low concentrations of TNFα enhanced excitatory synaptic strength while not affecting inhibitory neurotransmission. At higher concentrations, TNFα increased inhibitory neurotransmission without affecting excitatory synaptic strength. Both low and high concentrations of TNFα induced the synaptic accumulation of GluA1-containing AMPA receptors, suggesting that a high concentration of TNFα exerts a homeostatic effect on excitatory neurotransmission that prevents synaptic strengthening. Consistent with this, high, but not low, concentrations of TNFα activated microglia. Moreover, high concentrations of TNFα enhanced excitatory neurotransmission in microglia-depleted tissue cultures. These findings extend our knowledge on the role of TNFα on synaptic plasticity by demonstrating concentration-dependent effects on excitatory and inhibitory neurotransmission. They reveal a TNFα-mediated negative feedback mechanism on excitatory neurotransmission that is dependent on the activation of microglia, thereby emphasizing their role as gatekeepers of TNFα-mediated plasticity and homeostasis.
BANKSY: A Spatial Omics Algorithm that Unifies Cell Type Clustering and Tissue Domain Segmentation
Authors: Singhal Vipul , Chou Nigel , Lee Joseph , Liu Jinyue , Chock Wan Kee , Lin Li , Chang Yun-Ching , Teo Erica , Lee Hwee Kuan , Chen Kok Hao , Prabhakar Shyam
Published: April 2022

Each cell type in a solid tissue has a characteristic transcriptome and spatial arrangement, both of which are observable using modern spatial omics assays. However, the common practice is still to ignore spatial information when clustering cells to identify cell types. In fact, spatial location is typically considered only when solving the related, but distinct, problem of demarcating tissue domains (which could include multiple cell types). We present BANKSY, an algorithm that unifies cell type clustering and domain segmentation by constructing a product space of cell and neighbourhood transcriptomes, representing cell state and microenvironment, respectively. BANKSY’s spatial kernel-based feature augmentation strategy improves per-formance and scalability on both tasks when tested on FISH-based and sequencing-based spatial omics data. Uniquely, BANKSY identified hitherto undetected niche-dependent cell states in two mouse brain regions. Lastly, we show that quality control of spatial omics data can be formulated as a domain identification problem and solved using BANKSY. BANKSY represents a biologically motivated, scalable, and versatile framework for analyzing spatial omics data.
Dcifer: an IBD-based method to calculate genetic distance between polyclonal infections
Authors: Gerlovina Inna , Gerlovin Boris , Rodríguez-Barraquer Isabel , Greenhouse Bryan
Published: April 2022

An essential step toward reconstructing pathogen transmission and answering epidemiologically relevant questions from genomic data is obtaining pairwise genetic distance between infections. For recombining organisms such as malaria parasites, relatedness measures quantifying recent shared ancestry would provide a meaningful distance, suggesting methods based on identity by descent (IBD). While the concept of relatedness and consequently an IBD approach is fairly straightforward for individual parasites, the distance between polyclonal infections, which are prevalent in malaria, presents specific challenges and awaits a general solution that could be applied to infections of any clonality and accommodate multiallelic (e.g. microsatellite or microhaplotype) and biallelic (SNP) data. Filling this methodological gap, we present Dcifer (Distance for complex infections: fast estimation of relatedness), a method for calculating genetic distance between polyclonal infections, which is designed for unphased data, explicitly accounts for population allele frequencies and complexity of infection, and provides reliable inference. Dcifer’s IBD-based framework allows us to define model parameters that represent interhost relatedness and to propose corresponding estimators with attractive statistical properties. By using combinatorics to account for unobserved phased haplotypes, Dcifer is able to quickly process large datasets and estimate pairwise relatedness along with measures of uncertainty. We show that Dcifer delivers accurate and interpretable results and detects related infections with statistical power that is 2-4 times greater than that of approaches based on identity by state. Applications to real data indicate that relatedness structure aligns with geographic locations. Dcifer is implemented in a comprehensive publicly available software package.
The shape of aroma: measuring and modeling citrus oil gland distribution
Authors: Amézquita Erik J. , Quigley Michelle Y. , Ophelders Tim , Seymour Danelle , Munch Elizabeth , Chitwood Daniel H.
Published: April 2022

Citrus come in diverse sizes and shapes, and play a key role in world culture and economy. Citrus oil glands in particular contain essential oils which include plant secondary metabolites associated with flavor and aroma. Capturing and analyzing nuanced information behind the citrus fruit shape and its oil gland distribution provides a morphology-driven path to further our insight into phenotype-genotype interactions.

We investigated the shape of citrus fruit of 51 accessions based on 3D X-ray CT scan reconstructions. Accessions include all three ancestral citrus species, accessions from related genera, and several interspecific hybrids. We digitally separate and compare the size of fruit endocarp, mesocarp, exocarp, and oil gland tissue. Based on the centers of the oil glands, overall fruit shape is approximated with an ellipsoid. Possible oil gland distributions on this ellipsoid surface are explored using directional statistics.

There is a strong allometry along fruit tissues; that is, we observe a strong linear relationship between the volume of any pair of major tissues. This suggests that the relative growth of fruit tissues with respect to each other follows a power law. We also observe that on average, glands distance themselves from their nearest neighbor following a square root relationship, which suggests normal diffusion dynamics at play.

The observed allometry and square root models point to the existence of biophysical developmental constraints that govern novel relationships between fruit dimensions from both evolutionary and breeding perspectives. Understanding these biophysical interactions prompt an exciting research path on fruit development and breeding.

Societal Impact Statement

Citrus are intrinsically connected to human health and culture, including preventing human diseases like scurvy, and inspiring sacred rituals. Citrus fruits come in a stunning number of different sizes and shapes, ranging from small clementines to oversized pummelos, and fruits display a vast diversity of flavors and aromas. These qualities are key in both traditional and modern medicine and the production of cleaning and perfume products. By quantifying and modeling overall fruit shape and oil gland distribution, we can gain further insight into citrus development and the impacts of domestication and improvement on multiple characteristics of the fruit.
First clinical validation of whole genome screening on standard trophectoderm biopsies of preimplantation embryos
Authors: Xia Yuntao , Chertman Willy , Chandramohan Dhruva , Katz Maria , Bechor Elan , Podgursky Ben , Hoxie Michael , Zhang Qinnan , Kang Jessica , Blue Edwina , Chen Justin , Schleede Justin , Slotnick Nathan , Du Xiaoli , Kort Jonathan , Boostanfar Robert , Urcia Eric , Behr Barry , Siddiqui Noor
Published: April 2022

Whole Genome Sequencing (WGS) is used in healthcare and in the clinic, with the notable exception of preimplantation genetic testing (PGT). In PGT, only a few cells are available for sequencing, requiring DNA amplification which reduces data quality, sequence fidelity and sharply limits subsequent clinical impact. Here we demonstrate the first clinical validation of WGS on embryo biopsies using our lab development protocol, opening the door to broad use of WGS in fertility. We find that amplified DNA with comparable sensitivity and specificity to genomic DNA when performing whole genome sequencing assays. DNA amplification on cell lines and donated human embryos had an amplification success rate of >99.9% and 98.2% respectively and accuracy on both was >99.9% on aneuploidy status. GIAB samples (Genome in the Bottle reference NA12878) showed that our amplified DNA was broadly comparable to genomic DNA (99.99% accuracy, 99.99% specificity, 98.0% sensitivity and 98.1% precision). Using our assay, we were able to call variants, detect mitochondrial heteroplasmy, perform high precision screening without access to parental genomes, detect compound heterozygous variants, and score microdups/dels and uniparental disomies (to reduce risk of diseases such as DiGeorge syndrome and Prader-Willi syndrome). Our clinical study suggests that the full spectrum of traditional clinical genome bioinformatics, so far reserved to large samples, can now be performed on embryos before implantation.
Scan-Centric, Frequency-Based Method for Characterizing Peaks from Direct Injection Fourier transform Mass Spectrometry Experiments
Authors: Flight Robert M , Mitchell Joshua M , Moseley Hunter NB
Published: April 2022

We introduce a novel, scan-centric method for characterizing peaks from direct injection multi-scan Fourier transform mass spectra of complex samples that utilizes frequency values derived directly from the spacing of raw m/z points in spectral scans. Our peak characterization method utilizes intensity independent noise removal and normalization of scan-level data to provide a much better fit of relative intensity to natural abundance probabilities for low abundance isotopologues that are not present in all of the acquired scans. Moreover, our method calculates both peak- and scan-specific statistics incorporated within a series of quality control steps that are designed to robustly derive peak centers, intensities and intensity ratios with their scan-level variances. These cross-scan characterized peaks are suitable for use in our previously published peak assignment methodology, Small Molecule Isotope Resolved Formula Enumeration (SMIRFE).
Compendium-wide analysis of P. aeruginosa core and accessory genes reveal more nuanced transcriptional patterns
Authors: Lee Alexandra J. , Doing Georgia , Neff Samuel L. , Reiter Taylor , Hogan Deborah A. , Greene Casey S.
Published: April 2022

Strains of Pseudomonas aeruginosa, an opportunistic pathogen that causes difficult to treat infections, have significant genomic heterogeneity including the presence of diverse accessory genes that are only present in some strains or clades. Both core genes, which are conserved across strains, and accessory genes have been associated with traits such as biofilm formation and virulence. Much of what we know about core and accessory gene content comes from genome analyses. Here, we use a newly assembled transcriptome compendium to analyze the transcriptional patterns of core and accessory gene expression in PAO1 and PA14 strains across thousands of samples from hundreds of distinct experiments. We found that a subset of core genes were stable, having consistent correlated expression patterns across samples regardless of strain background, with a focus on strains PAO1 and PA14. These stable core genes had fewer co-expressed neighbors that were accessory genes.

Significance

Pseudomonas aeruginosa is a ubiquitous pathogen. There is a lot of diversity amongst P. aeruginosa strains, some which are clinically relevant. Understanding how these different strain-level traits manifest is important for identifying targets that regulate different traits of interest. With the availability of a PAO1-mapped and PA14-mapped RNA-seq compendium, which contain hundreds of strains, it is now possible to examine the effect of different strains on expression, which can mediate different traits. In this study we developed an approach to compare expression profiles across different P. aeruginosa gene groups – core and accessory genes. This approach revealed a subset of core genes with different transcriptional patterns across strains, which could contribute to trait differences.
A new chemotype of chemically tractable nonsteroidal estrogens based on a thieno[2,3-d]pyrimidine core
Authors: Sammeta Vamshikrishna Reddy , Norris John D. , Artham Sandeep , Torrice Chad D. , Byemerwa Jovita , Joiner Carstyn , Fanning Sean W. , McDonnell Donald P. , Willson Timothy M.
Published: April 2022

Despite continued interest in development of nonsteroidal estrogens and antiestrogens, there are only a few chemotypes of estrogen receptor ligands. Using targeted screening in a ligand sensing assay we identified a phenolic thieno[2,3-d]pyrimidine with affinity for estrogen receptor α. An efficient three-step synthesis of the heterocyclic core and structure-guided optimization of the substituents resulted in a series of potent nonsteroidal estrogens. The chemical tractability of the thieno[2,3-d]pyrimidine chemotype will support the design of new estrogen receptor ligands as therapeutic hormones and antihormones.

GRAPHICAL ABSTRACT
Habitat preference influences response to changing agricultural landscapes in two long-horned bees
Authors: Hirayama Gaku S. , Ushimaru Atushi
Published: April 2022

Agricultural intensification and urban development have drastically influenced pollinators living in semi-natural grasslands. Pollinators are likely to have different responses to these land-use changes; some decline rapidly while others maintain or increase their populations. We predicted differences in interspecific response to land-use changes are partly attributed to differences in habitat preference. We examined the distribution and flower use patterns of two closely relatedEuceraspecies with different habitat preferences. Study sites were meadows surrounding traditional, intensified, and urbanised agricultural lands in the Osaka-Kobe metropolitan area, Japan. Forest-associatedEucera nipponensiswere significantly fewer in consolidated and urbanised meadows than traditional meadows, whereas open land-associatedE. spurcatipesexhibited the opposite. A significant negative relationship between their abundances was also found. Both species foraged on legume flowers most frequently (83.5%), but floral use pattern was significantly different in traditional and consolidated meadows. Bee species preferring stable habitats were vulnerable to land consolidation and urbanisation, while species associated with disturbed habitats maintained or increased population size in meadows with the land-use changes. Thus, recent land uses may have different impacts on species with different habitat preferences.
High total water loss driven by low-fat diet in desert-adapted mice
Authors: Blumstein Danielle M. , Colella Jocelyn P. , Linder Ernst , MacManes Matthew D.
Published: April 2022

Availability of food resources is an important driver of survival. Animals must either relocate or adapt to persist in environments where critical resource abundance is changing. An optimal diet balances energy gain, water regulation, and nutrition. We used flow-through respirometry to characterize metabolic phenotypes of the desert-adapted cactus mouse (Peromyscus eremicus) under diurnally variable environmental conditions that mimic the environment of the Sonoran Desert. We treated mice with two different energetically equivalent diets, a standard diet and a low-fat diet, and measured energy expenditure, water loss rate, respiratory quotient, weight, and electrolyte levels. Mice fed the low-fat diet lost significantly more water than those on the standard diet. Our results suggest that cactus mice may have limited capacity to tolerate water deprivation if optimal foods become less abundant. Given that climate change is predicted to modify the distribution of food items, understanding these links may have important implications for long-term population viability for desert and non-desert adapted animals alike.