bluuebunny/crossref_metadata_2025 huggingface dataset:
SeedTransNet: a directional translational network revealing regulatory patterns during seed maturation and germination
Authors: Bai Bing , Schiffthaler Bastian , van der Horst Sjors , Willems Leo , Vergara Alexander , Karlström Jacob , Mähler Niklas , Delhomme Nicolas , Bentsink Leónie , Hanson Johannes
Published: October 2022

Seed maturation is the developmental process that prepares the embryo for the desiccated waiting period before germination. It is associated with a series of physiological changes leading to the establishment of seed dormancy, seed longevity, and desiccation tolerance. We studied translational changes during seed maturation and observed a gradual reduction in global translation during seed maturation. Transcriptome and translatome profiling revealed specific reduction in the translation of thousands of genes. By including previously published data on germination and seedling establishment, a regulatory network based on polysome occupancy data was constructed: SeedTransNet. Network analysis predicted translational regulatory pathways involving hundreds of genes with distinct functions. The network identified specific transcript sequence features suggesting separate translational regulatory circuits. The network revealed several seed maturation-associated genes as central nodes, and this was confirmed by specific seed phenotypes of the respective mutants. One of the regulators identified, an AWPM19 family protein, PM19-Like1 (PM19L1), was shown to regulate seed dormancy and longevity. This putative RNA-binding protein also affects the translational regulation of its target mRNA, as identified by SeedTransNet. Our data show the usefulness of SeedTransNet in identifying regulatory pathways during seed phase transitions.
Global ubiquitinome analysis reveals the role of E3 ubiquitin ligase FaBRIZ in strawberry fruit ripening
Authors: Wang Yuying , Kong Lingxi , Wang Weihao , Qin Guozheng
Published: October 2022

Ubiquitination is an important post-translational modification that mediates protein degradation in eukaryotic cells, participating in multiple biological processes. However, the profiling of protein ubiquitination and the function of this crucial modification in fruit ripening remain largely unknown. In this study, we found that suppression of proteasome by the inhibitor MG132 retarded strawberry fruit ripening. Using K-ɛ-GG antibody enrichment combined with high-resolution mass spectrometry, we performed a comprehensive ubiquitinome analysis in strawberry fruit. We identified 2947 ubiquitination sites for 2878 peptides within 1487 proteins, which are involved in a variety of cellular functions. The lysine at position 48 (K48)-linked poly-ubiquitin chains appeared to be the most prevalent type of modification among the identified ubiquitinated proteins. A large number of ubiquitination sites exhibited altered ubiquitination levels after proteasome inhibition, including those within ripening-related proteins associated with sugar and acid metabolism, cell wall metabolism, anthocyanin synthesis, and ABA biosynthesis and signalling. We further demonstrated that FaBRIZ, a RING-type E3 ligase, functions as a negative regulator of ripening in strawberry fruit. Our findings highlight the critical regulatory roles of protein ubiquitination in fruit ripening. The ubiquitinome data provide a basis for further exploration of the function of ubiquitination on specific proteins.
A study of the magnetic activity and variability of GJ 436
Authors: Kumar M , Fares R
Published: October 2022

We present a magnetic activity study of GJ 436 using spectroscopic data from HARPS, spanning over 14 yr, and additional data from NARVAL, falling within the HARPS observations. We study the Ca ii H&K, He i D3, Na i doublet, H α, and Ca ii IRT triplets lines and explore linear correlations between them. Using the full HARPS data set, we found indices H α versus Ca ii H&K & H α versus He i to correlate positively. From the NARVAL data set, covering one observing epoch, we found Ca ii IRT3 versus Ca ii IRT2 & Ca ii IRT3 versus H α index to correlate negatively. We investigate long and short-term periodicity in these index variations, using the Generalized Lomb–Scargle periodogram. For Ca ii H&K, Na i and H α indices, we detect long-term periods of 2470.7 d (∼ 6.8 yr), 1861.6 d (∼ 5.1 yr), and 2160.9 d (∼ 5.9 yr) respectively, consistent with GJ 436’s photometric cycle of ∼ 7.4 yr. Applying the ‘Pooled Variance’ technique to H α & Na i indices, we found ∼ 2500 d to be the period of an activity cycle mechanism, in good agreement with the detected 2470.7 d period. For Ca ii H&K and H α indices, we detect short-term periods of $39.47^{+0.11}_{-0.15}$ d and $40.46^{+0.44}_{-0.52}$ d, respectively, identified as the stellar rotation period. The stellar rotation is detected after pre-whitening the long-term periodicity. It is detected as well in the analysis of individual observing epochs.
Torque reversals and wind variations of X-ray pulsar Vela X-1
Authors: Liao Zhenxuan , Liu Jiren , Gou Lijun
Published: October 2022

The erratic spin history of Vela X-1 shows some continuous spin-up/spin-down trend over tens of days. We study the orbital profile and spectral property of Vela X-1 in these spin-up/spin-down intervals, using the spin history monitored by Fermi/GBM and light curve from Swift/BAT and MAXI/GSC. The BAT fluxes in the spin-up intervals are about 1.6 times those of the spin-down intervals for out-of-eclipse orbital phases. The spin-up intervals also show a higher column density than the spin-down intervals, indicating that there is more material on the orbital scale for the spin-up intervals. It could be due to the variation of the stellar wind of the optical star (HD 77581) on tens of days. The varying wind could lead to alternating prograde/retrograde accreting flow to the neutron star, which dominates the transfer of the angular momentum to Vela X-1, but not the total observed luminosity.
Efficacy of belimumab in patients with systemic lupus erythematosus from North East Asia: Results of exploratory subgroup analyses
Authors: Zheng Jie , Gu Jieruo , Su Yin , Li Yang , Li Xingfu , Xiong Cui , Cao Hua , Quasny Holly , Chu Myron , Curtis Paula , DeRose Kathleen , Kurrasch Regina , Meizlik Paige , Roth David A , Zhang Fengchun
Published: October 2022

Objectives

To assess belimumab efficacy in patients from North East Asia (NEA) with systemic lupus erythematosus (SLE) in baseline demographic/disease characteristic subgroups.

Methods

This analysis of patient subgroups from BLISS-NEA (GSK Study 113750; NCT01345253) studied adults with SLE randomized to belimumab (10 mg/kg intravenous) or placebo. Primary endpoint, SLE Responder Index 4 (SRI-4) response rate at Week 52, was analysed in subgroups defined by gender, country, prednisone-equivalent dose, concomitant medications, Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, complement (C) levels, anti-double-stranded deoxyribonucleic acid (dsDNA) positivity, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score.

Results

Patients (overall population: N = 677; belimumab: n = 451, placebo: n = 226) were from China (76.4%), Korea (14.8%), and Japan (8.9%). The mean age was 32.1 years; 92.9% were female. In the overall population, more belimumab (53.8%) than placebo (40.1%) patients were SRI-4 Week 52 responders (p = .0001). SRI-4 response rates by subgroups were generally consistent with the overall population. A greater response with belimumab was seen in patients with a baseline SELENA-SLEDAI score ≥10 versus ≤9 and patients with low C3/C4 levels and anti-dsDNA positive at baseline versus those ‘NOT’ (low C3 and/or C4 and anti-dsDNA positive).

Conclusions

These findings continue to support the efficacy of belimumab in SLE.
Trimethoprim-sulfamethoxazole and the risk of a hospital encounter with hyperkalemia: a matched population-based cohort study
Authors: Hwang Y Joseph , Muanda Flory T , McArthur Eric , Weir Matthew A , Sontrop Jessica M , Lam Ngan N , Garg Amit X
Published: October 2022

Background

Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX versus amoxicillin and determined if this risk is modified by a patient's baseline kidney function [estimated glomerular filtration rate (eGFR)].

Methods

We conducted a population-based cohort study in Ontario, Canada involving adults ≥66 years of age newly treated with TMP-SMX (n = 58 999) matched 1:1 with those newly treated with amoxicillin (2008–2020). The primary outcome was a hospital encounter with hyperkalemia defined by a laboratory serum potassium value ≥5.5 mmol/L within 14 days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury (AKI) and all-cause hospitalization. Risk ratios (RRs) were obtained using a modified Poisson regression.

Results

A hospital encounter with hyperkalemia occurred in 269/58 999 (0.46%) patients treated with TMP-SMX versus 80/58 999 (0.14%) in those treated with amoxicillin {RR 3.36 [95% confidence interval (CI) 2.62–4.31]}. The absolute risk of hyperkalemia in patients treated with TMP-SMX versus amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for an eGFR ≥60 ml/min/1.73 m2, 0.42% for eGFR 45–59, 0.85% for eGFR 30–44 and 1.45% for eGFR <30; additive interaction P < .001). TMP-SMX versus amoxicillin was associated with a higher risk of a hospital encounter with AKI [RR 3.15 (95% CI 2.82–3.51)] and all-cause hospitalization [RR 1.43 (95% CI 1.34–1.53)].

Conclusions

The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX versus amoxicillin and the risk was highest in patients with a low eGFR.
A comprehensive survey of bat sarbecoviruses across China in relation to the origins of SARS-CoV and SARS-CoV-2
Authors: Wu Zhiqiang , Han Yelin , Wang Yuyang , Liu Bo , Zhao Lamei , Zhang Junpeng , Su Haoxiang , Zhao Wenliang , Liu Liguo , Bai Shibin , Dong Jie , Sun Lilian , Zhu Yafang , Zhou Siyu , Song Yiping , Sui Hongtao , Yang Jian , Wang Jianwei , Zhang Shuyi , Qian Zhaohui , Jin Qi
Published: October 2022

SARS-CoV and SARS-CoV-2 have been thought to originate from bats. In this study, we screened pharyngeal and anal swabs from 13 064 bats collected between 2016 and 2021 at 703 locations across China for sarbecoviruses, covering almost all known southern hotspots, and found 146 new bat sarbecoviruses. Phylogenetic analyses of all available sarbecoviruses show that there are three different lineages—L1 as SARS-CoV-related CoVs (SARSr-CoVs), L2 as SARS-CoV-2-related CoVs (SC2r-CoVs) and novel L-R (recombinants of L1 and L2)—present in Rhinolophus pusillus bats, in the mainland of China. Among the 146 sequences, only four are L-Rs. Importantly, none belong in the L2 lineage, indicating that circulation of SC2r-CoVs in China might be very limited. All remaining 142 sequences belong in the L1 lineage, of which YN2020B-G shares the highest overall sequence identity with SARS-CoV (95.8%). The observation suggests endemic circulations of SARSr-CoVs, but not SC2r-CoVs, in bats in China. Geographic analysis of the collection sites in this study, together with all published reports, indicates that SC2r-CoVs may be mainly present in bats of Southeast Asia, including the southern border of Yunnan province, but absent in all other regions within China. In contrast, SARSr-CoVs appear to have broader geographic distribution, with the highest genetic diversity and sequence identity to human sarbecoviruses along the southwest border of China. Our data provide the rationale for further extensive surveys in broader geographical regions within, and beyond, Southeast Asia in order to find the most recent ancestors of human sarbecoviruses.
Teenage conduct problems: a lifetime of disadvantage in the labour market?
Authors: Parsons Sam , Bryson Alex , Sullivan Alice
Published: October 2022

Using data from British cohorts born in 1958 and 1970, we used quantile regression to investigate the impact of ‘mild’ and ‘severe’ teenage conduct problems on months spent in paid employment or paid employment, education, and training (EET) between ages 17 and 42. Those with conduct problems spent significantly less time in employment or EET by age 42. The penalty grows in one’s 20s and tends to persist thereafter. Among men, the participation gap was greatest among those with ‘severe’ teenage conduct problems and among those in the lower half of the participation distribution. There was no participation penalty arising from teenage conduct problems among the older generation of men in the top quartile of the participation distribution. Among women, conduct problems were associated with less time in employment and EET across the whole distribution of the participation distribution, and these penalties were greatest for women in the younger 1970 cohort.
Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases
Authors: Chen Tempe K , Batra Jagmohan S , Michalik David E , Casillas Jacqueline , Patel Ramesh , Ruiz Maritza E , Hara Harneet , Patel Bhavita , Kadapakkam Meena , Ch'Ng James , Small Catherine B , Zagaliotis Panagiotis , Ragsdale Carolyn E , Leal Luis O , Roilides Emmanuel , Walsh Thomas J
Published: October 2022

Background

Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).

Methods

The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted.

Results

Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response).

Conclusions

Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.
Gender, Political Dynasties, and Committee Assignments: Evidence From Indonesia
Authors: Prihatini Ella , Halimatusa’diyah Iim
Published: October 2022

The persistence of political dynasties in developed and developing countries has been an interesting puzzle as democracy does not automatically obliterate the domination of familial ties in politics. Prior studies suggest that women are more likely to be dynastic than men. However, it remains unclear on how parties are allocating dynasts into committees and whether it is gendered or not. This paper introduces new observational data on female parliamentary representation, dynastic background and committee membership of 575 sitting parliamentarians in Indonesia. The findings suggest that one in every four members of parliament are dynasts and the proportion among female lawmakers has increased from 42% in 2009 to 44% in 2019. However, the experience of dynastic women in relation to committee assignment is not uniform. The critical variable that influences their placement appears to be the political party to which they belong, particularly in terms of nomination and internal structure. This paper offers initial leads for future research endeavours in connecting the intersectionality between political dynasties and committee assignments in other countries.
Auxin Crosstalk with Reactive Oxygen and Nitrogen Species in Plant Development and Abiotic Stress
Authors: Parveen Nishat , Kandhol Nidhi , Sharma Shivesh , Singh Vijay Pratap , Chauhan Devendra Kumar , Ludwig-Müller Jutta , Corpas Francisco J , Tripathi Durgesh Kumar
Published: October 2022

The phytohormone auxin acts as an important signaling molecule having regulatory functions during the growth and development of plants. Reactive oxygen species (ROS) are also known to perform signaling functions at low concentrations; however, over-accumulation of ROS due to various environmental stresses damages the biomolecules and cell structures and leads to cell death, and therefore, it can be said that ROS act as a double-edged sword. Nitric oxide (NO), a gaseous signaling molecule, performs a wide range of favorable roles in plants. NO displays its positive role in photomorphogenesis, root growth, leaf expansion, seed germination, stomatal closure, senescence, fruit maturation, mitochondrial activity and metabolism of iron. Studies have revealed the early existence of these crucial molecules during evolution. Moreover, auxin, ROS and NO together show their involvement in various developmental processes and abiotic stress tolerance. Redox signaling is a primary response during exposure of plants to stresses and shows a link with auxin signaling. This review provides updated information related to crosstalk between auxin, ROS and NO starting from their evolution during early Earth periods and their interaction in plant growth and developmental processes as well as in the case of abiotic stresses to plants.
Behavior of Photosystems II and I Is Modulated Depending on N Partitioning to Rubisco in Mature Leaves Acclimated to Low N Levels and Senescent Leaves in Rice
Authors: Suzuki Yuji , Ohsaki Kaho , Takahashi Yuki , Wada Shinya , Miyake Chikahiro , Makino Amane
Published: October 2022

In mature leaves acclimated to low N levels and in senescent leaves, photosystems II and I (PSII and PSI, respectively) show typical responses to excess light energy. As CO2 assimilation is not transiently suppressed in these situations, the behavior of PSII and PSI is likely caused by endogenous biochemical changes in photosynthesis. In this study, this subject was studied in rice (Oryza sativa L.). Analysis was performed on mature and senescent leaves of control and N-deficient plants. Total leaf-N, Rubisco and chlorophyll (Chl) levels and their ratios were determined as biochemical parameters of photosynthesis. Total leaf-N, Rubisco and Chl levels decreased in the mature leaves of N-deficient plants and senescent leaves. The percentage of Rubisco-N in the total leaf-N decreased in these leaves, whereas that of Chl-N tended to remain almost constant in mature leaves but increased in senescent leaves. Changes in PSII and PSI parameters were best accounted for by the Rubisco-N percentage, strongly suggesting that the behavior of PSII and PSI is modulated depending on changes in N partitioning to Rubisco in mature leaves acclimated to low N levels and in senescent leaves. It is likely that a decrease in N partitioning to Rubisco leads to a decrease in Rubisco capacity relative to other photosynthetic capacities that inevitably generate excess light energy and that the operation of PSII and PSI is modulated in such situations.
Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia
Authors: Li Jian , Gong Sheng-Hui , He Yun-Ling , Cao Yan , Chen Ying , Huang Guang-Hai , Wang Yu-Fei , Zhao Ming , Cheng Xiang , Zhou Yan-Zhao , Zhao Tong , Zhao Yong-Qi , Fan Ming , Wu Hai-Tao , Zhu Ling-Ling , Wu Li-Ying
Published: October 2022

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.
The Timing of Elections and Neonatal Mortality: Evidence from India
Authors: Bhattacharjee Shampa
Published: October 2022

This paper uncovers evidence of political cycles in developmental outcomes in the Indian context. Comparing children born to the same mother, it shows that children born 0–11 months before scheduled state legislative assembly elections have a significantly lower risk of neonatal mortality. The effect of being born just before elections is higher in politically more competitive regions. The paper provides some evidence of the channels behind this result. The usage of prenatal care increases before elections and mothers of children born before elections are more likely to have antenatal checkups and tetanus injections during pregnancy. Components of antenatal checkups, like the probability of having a blood test or an abdominal examination during pregnancy, also increase before elections. The improvement in child health outcomes before elections seems to be driven by a transfer of resources from non-election to election years rather than an overall improvement in child health outcomes.
Integrative taxonomic analysis of new collections from the central Angolan highlands resolves the taxonomy of African pipistrelloid bats on a continental scale
Authors: Taylor Peter John , Strydom Erika , Richards Leigh , Markotter Wanda , Toussaint Dawn Cory , Kearney Teresa , Cotterill F P D (Woody) , Howard Alexandra , Weier Sina Monika , Keith Mark , Neef Gӧtz , Mamba Mnqobi L , Magagula Siphesihle , Monadjem Ara
Published: October 2022

Ten years ago, the genus-level and species-level taxonomy of African pipistrelloid bats was in a state of flux. In spite of advances in the past decade, gaps in collecting from species-rich regions like Angola have hampered efforts to revise this group. We report on new collections of pipistrelle-like bats from the poorly sampled central highlands of Angola (1000–1500 m a.s.l.) as well as comparative material from lower-lying areas of Eswatini and South Africa. Specimens identified as Neoromicia anchietae, collected 400–700 km east of the holotype locality in the western highlands of Angola, were genetically and morphologically distinctive from N. anchietae s.l. from South Africa and Eswatini. We describe herein this latter lineage as a distinct species from low-lying areas of south-eastern Africa, distinct from N. anchietae s.s., which is therefore restricted to the central and western Angolan highlands. We also identified shallow to deep genetic divergence between different African regions in other recognized pipistrelloid species, such as conspecificity between the long-eared species Laephotis angolensis from Angola and Laephotis botswanae from northern Botswana, northern Namibia and south-western Zambia. Our phylogeny supports a recently proposed generic classification of African pipistrelloid bats.
Late Spontaneous Postradial Keratotomy Corneal Perforation After Scleral Contact Lens Use—Case Report
Authors: Weber Sarah La Porta , Jorge Bianca Carneiro de Melo , Mourão Ana Beatriz Gurgel , Hofling-Lima Ana Luisa
Published: October 2022

Purpose:

To describe a case of late spontaneous postradial keratotomy corneal perforation after scleral contact lens (SCL) wear for optic correction.

Setting:

Tertiary referral center for corneal pathology.

Design:

Case report.

Results:

A 64-year-old man presented the consequences of a late radial keratotomy (RK) surgery performed for myopia correction 26 years ago. His ophthalmologic history was a RK in both eyes (BE), previous Lasik surgery in BE and Lasik enhancement in the right eye (RE), and pterygium excision with conjunctival transplantation in RE. To improve visual acuity, SCL were fitted in both eyes. After 8 months of use, on a certain day, when removing the lens from the RE, the patient reported experiencing intense eye pain and reduced visual acuity. On ophthalmologic examination, the RE cornea was perforated in one of the previous RK incisions. An urgent corneal transplant was performed in the RE, followed by cataract surgery in the same eye.

Conclusion:

Corneal instability caused by RK scars and daily manipulation with the SCL use may have led to ocular perforation.
Student Confidence and Interest in Acute Care Physical Therapy Through Peer Simulation
Authors: Neely Laurie C. , Beato Morris , Viana Samantha , Ayala Sol , Brari Nensi , Pabian Patrick
Published: October 2022

Introduction:

The COVID-19 pandemic caused various challenges to the academic setting, especially for health care programs that require face-to-face (F2F) interactions to learn psychomotor skills. Simulation is often used to integrate didactic knowledge and enhance psychomotor skills to prepare students for clinical education experiences. The purpose of this study was to compare student confidence and interest in setting type prior to a first clinical education experiences between students who completed an F2F peer simulation course and students who completed the course virtually.

Methods:

Subjects included second-year doctor of physical therapy students who participated in the F2F course in 2019 (n = 37) and those who completed the virtual course in 2020 (n = 36). A 5-item pre- and postcourse self-assessment was administered to evaluate student confidence and interest in the acute care setting. A factorial analysis of variance was used to examine confidence scores of both cohorts at pre- and postcourse assessment.

Results:

Confidence rating of students from both cohorts significantly improved from precourse to postcourse in all areas, indicating that all students showed improved perceived confidence in their clinical skills upon completion of the course. However, the ratings of “ability to respond to changes in patient status in the acute care setting” were significantly greater in the F2F cohort than in the virtual cohort at the end of the course. There was also a positive interaction effect of cohort year (delivery mode) indicating that the F2F cohort had a stronger response in level of perceived confidence compared with the virtual cohort. In addition, student interest in the acute care setting was significantly greater at postcourse assessment for students from both cohorts.

Conclusion:

Postcourse rating of student-perceived confidence in clinical skills performance and interest in the acute care setting improved regardless of the mode of delivery of the course. However, when examining student-perceived confidence levels to respond to change in patient status, students who participated in the F2F course felt more confident in their ability to do so. Although perceived confidence levels improved for all students, virtual learning of clinical skills may not be as effective in training students to safely treat complex patients in the acute care setting.
Updates in functional dyspepsia and bloating
Authors: Lacy Brian E. , Cangemi David J.
Published: October 2022

Purpose of review

Functional dyspepsia and bloating are common gastrointestinal conditions that frequently lead to gastroenterology referral. Both disorders have a significant negative impact on patients’ quality of life and the healthcare system. The purpose of this review is to highlight important new findings in the cause, pathophysiology and treatment of these two disorders.

Recent findings

Confocal laser endomicroscopy identified changes in epithelial barrier structure and function, providing important insights into the development of functional dyspepsia symptoms when combined with new observations of localized duodenal inflammation. Changes in the gut microbiome may be responsible for functional dyspepsia symptoms in some patients and may respond to gut-selective antibiotics. New data from the NIH-sponsored Gastroparesis Consortium confirmed that functional dyspepsia and gastroparesis are not distinct disorders but rather exist on a spectrum. Virtual reality may be a new therapeutic option for the treatment of functional dyspepsia. A novel questionnaire was developed and validated to assess symptoms, prevalence and impact in patients with bloating and distension. A meta-analysis identified medications to treat symptoms of bloating in patients with irritable bowel syndrome and constipation.

Advances in our understanding of the pathophysiology of functional dyspepsia and bloating are leading to important changes in medical therapies.
Working Memory and Processing Speed Predict Math Skills in Pediatric Brain Tumor Survivors
Authors: Peterson Rachel K. , Ng Rowena , Ludwig Natasha N. , Jacobson Lisa A.
Published: October 2022

Objective:

Childhood brain tumor (BT) survivors are at risk for working memory (WM) and processing speed (PS) deficits, which impact other cognitive domains. This study aimed to characterize WM, PS, and untimed mathematics calculation performance in pediatric BT survivors at least 2 years post-diagnosis, identify medical factors associated with deficits in mathematics, and examine whether WM and/or PS predict mathematics performance in this clinical sample.

Methods:

Retrospective data were gathered from 72 BT survivors between 7 and 21 years of age (M=13.64 y, SD=4.01 y) for a clinical neuropsychologic evaluation. All participants completed Wechsler measures of WM and PS and a measure of untimed mathematics calculation.

Results:

WM, PS, and the mathematics calculation were significantly lower than the normative mean. Math scores were not correlated with any of the examined medical factors. PS was negatively correlated with the Neurological Predictor Scale and positively correlated with age at diagnosis. Both WM and PS were associated with math outcomes and accounted for 30.4% and 19.2% of the variance, respectively.

Conclusions:

The findings indicate that WM and PS contribute to mathematics performance in pediatric BT survivors. Examining mathematics performance should be a part of clinical neuropsychological evaluations. Interventions to improve mathematics performance in this population should also focus on WM and compensatory strategies for slowed PS.
The Midfacial Soft Tissue Changes After Anterior Maxillary Segmental Distraction Osteogenesis in Patients With Cleft: A 3-Dimensional Volumetric-Based Subunit Analysis
Authors: Wan Teng , Sun Hao , Jiang Tengfei , Zhu Min , Wang Xudong
Published: October 2022

Background:

Maxillary hypoplasia is common in patients with cleft lip and palate. In this study, the authors investigated the soft tissue changes in midfacial regions after anterior maxillary segmental distraction osteogenesis (AMSDO) in patients with cleft.

Methods:

Eight patients with cleft lip and palate who underwent AMSDO were enrolled in this study. Spiral computed tomographic images were taken before surgery and 6–12 months after surgery to evaluate soft tissue changes after AMSDO. The midfacial area was divided into 6 regions of interest according to anatomical subunits. The average movements of each region were calculated using volumetric changes and preoperative region surface areas.

Results:

The upper lip on both sides has the most anterior movement (5.22±0.86 and 5.14±0.84 mm), supracommissural regions have a little less movement (4.11±0.55 and 3.81±0.67 mm), paranasal regions have the least movement (3.37±0.47 and 3.15±0.36 mm). The corresponding regions of interest showed no significant difference on the cleft side versus the noncleft side.

Conclusions:

Anterior maxillary segmental distraction osteogenesis can improve the soft tissue profile in patients with cleft, and there was no significant difference in soft tissue changes between the cleft side and the noncleft side.
PD-L1 activity is associated with partial EMT and metabolic reprogramming in carcinomas
Authors: Muralidharan Srinath , Sehgal Manas , Soundharya R , Mandal Susmita , Majumdar Sauma Suvra , Yeshwanth M , Saha Aryamaan , Jolly Mohit Kumar
Published: October 2022

Immune evasion and metabolic reprogramming are hallmarks of cancer progression often associated with a poor prognosis and frequently present significant challenge for cancer therapies. Recent studies have emphasized on the dynamic interaction between immunosuppression and the dysregulation of energy metabolism in modulating the tumor microenvironment to promote cancer aggressiveness. However, a pan-cancer association among these two hallmarks, and a potent common driver for them – Epithelial-Mesenchymal Transition (EMT) – remains to be done. Here, our meta-analysis across 184 publicly available transcriptomic datasets as well as The Cancer Genome Atlas (TCGA) data reveals that an enhanced PD-L1 activity signature along with other immune checkpoint markers correlate positively with a partial EMT and elevated glycolysis signature but a reduced OXPHOS signature in many carcinomas. These trends were also recapitulated in single-cell RNA-seq time-course EMT induction data across cell lines. Furthermore, across multiple cancer types, concurrent enrichment of glycolysis and PD-L1 results in worse outcomes in terms of overall survival as compared to enrichment for only PD-L1 activity or expression. Our results highlight potential functional synergy among these interconnected axes of cellular plasticity in enabling metastasis and/or multi-drug resistance in cancer.
Engineering Nanowires in Bacteria to Elucidate Electron Transport Structural-Functional Relationships
Authors: Myers Ben , Catrambone Francesco , Allen Stephanie , Hill Phil J , Kovacs Katalin , Rawson Frankie J
Published: October 2022

Bacterial pilin nanowires are protein complexes, suggested to possess electroactive capabilities forming part of the cells’ bioenergetic programming. Their role is thought to be linked to facilitating electron transfer with the external environment to permit metabolism and cell-to-cell communication. There is a significant debate, with varying hypotheses as to the nature of the proteins currently lying between type-IV pilin-based nanowires and polymerised cytochrome-based filaments. Importantly, to date, there is a very limited structure-function analysis of these structures within whole bacteria. In this work, we engineeredCupriavidus necatorH16, a model autotrophic organism to express differing aromatic modifications of type-IV pilus proteins to establish structure-function relationships on conductivity and the effects this has on pili structure. This was achievedviaa combination of high-resolution PeakForce tunnelling atomic force microscopy (PeakForce TUNA™) technology, alongside conventional electrochemical approaches enabling the elucidation of conductive nanowires emanating from whole bacterial cells for the first time. This work is the first example of functional type-IV pili protein nanowires produced under aerobic conditions using aCNchassis. This work has far-reaching consequences in understanding the basis of bio-electrical communication between cells and with their external environment.

Abstract Figure

Graphical abstract displaying theoretical PilA monomer models (left), PeakForce TUNA atomic force microscopy contact current images (right) of wild-type (top) and modified with increased tyrosine content (bottom) PilA filaments expressed byCupriavidus necatorH16 cells.
Towards modelling cold-water coral reef-scale crumbling: Including morphological variability in mechanical surrogate models
Authors: Fernández Marta Peña , Williams Josh , Büscher Janina V. , Titschack Jürgen , Roberts J Murray , Henninge Sebastian , Wolfram Uwe
Published: October 2022

The structural complexity of cold-water corals is threatened by ocean acidification. Increased porosity and weakening of structurally critical parts of the reef framework may lead to rapid physical collapse on an ecosystem scale, reducing their potential for biodiversity support. We can use computational models to describe the mechanisms leading to reef-crumbling. How-ever, the implementation of such models into an efficient predictive tool that allows us to determine risk and timescales of reef collapse is missing. Here, we identified possible surrogate models to represent the branching architecture of the cold-water coral speciesLophelia pertusa. For length scales greater than 13 cm, a continuum finite element mechanical approach can be used to analyse mechanical competence whereas at smaller length scales, mechanical surrogate models need to explicitly account for the statistical differences in the structure. We showed large morphological variations betweenL. pertusacolonies and branches, as well asdeadandliveskeletal structures, which need to be considered for the development of rapid monitoring tools for predicting risk of cold-water coral reefs crumbling. This will allow us to investigate timescales of changes, including the impact of exposure times to acidified waters on reef-crumbling.
canaper: Categorical analysis of neo- and paleo-endemism in R
Authors: Nitta Joel H. , Laffan Shawn W. , Mishler Brent D. , Iwasaki Wataru
Published: October 2022

Biodiversity has typically been quantified using species richness, but this ignores evolutionary history. Due to the increasing availability of robust phylogenies, methods have been developed that incorporate phylogenetic relationships into quantification of biodiversity. CANAPE (categorical analysis of neo- and paleo-endemism) is one such method that can provide insight into the evolutionary processes generating biodiversity. The only currently available software implementing CANAPE is Biodiverse, which is written in Perl and can be used either through a graphical user interface (GUI) or user-developed scripts. However, many researchers, particularly in the fields of ecology and evolutionary biology, use the R programming language to conduct their analyses.

Here, we present canaper, a new R package that provides functions to conduct CANAPE in R. canaper implements methods for efficient computation, including parallelization and encoding of community data as sparse matrices. The interface is designed for maximum simplicity and reproducibility; CANAPE can be conducted with two functions, and parallel computing can be enabled with one line of code.

Our case study shows that canaper produces equivalent results to Biodiverse and can complete computations on moderately sized datasets quickly (< 10 min to reproduce a canonical study).

canaper allows researchers to conduct all analyses from data import and cleaning through CANAPE within R, thereby averting the need to manually import and export data and analysis results between programs. We anticipate canaper will become a part of the toolkit for analyzing biodiversity in R.
PointedSDMs– an R package to help facilitate the construction of integrated species distribution models
Authors: Mostert Philip S. , O’Hara Robert B.
Published: October 2022

1

Integration of disparate datasets is a rapidly growing area in quantitative ecology, and is subsequently becoming a major asset in understanding the shifts and trends in species’ distributions.

However, the tools and software available to construct statistical models to integrate these disparate datasets into a unified framework is lacking, stagnating the growth of data integration in applications.

This paper presentsPointedSDMs: an easy to useRpackage used to construct integrated species distribution models using the integrated nested Laplace Approximation methodology.

The package is presented in this paper through an illustrative example for a selection of species found across Pennsylvania state.
Streetlights affect moth orientation beyond flight-to-light behaviour
Authors: Degen Jacqueline , Storms Mona , Lee Chengfa Benjamin , Jechow Andreas , Stöckl Anna Lisa , Hölker Franz , Jakhar Aryan , Walter Thomas , Walter Stefan , Mitesser Oliver , Hovestadt Thomas , Degen Tobias
Published: October 2022

One of the most dramatic changes occurring on our planet in recent decades is the ever-increasing extensive use of artificial light at night, which drastically altered the environment nocturnal animals are adapted to 1,2. One nocturnal species group experiencing marked declines are moths, which are not only of great importance for species conservation, but also for their key role in food webs and in ecosystem services such as nocturnal plant pollination 3,4. Light pollution has been identified as a driver in the dramatic insect decline of the past years 5–7, yet little is known about its impact on natural insect orientation behaviour. Using harmonic radar tracking, we show that the orientation of several species of moths is significantly affected by streetlights, although only 4 % of individuals showed flight-to-light behaviour. We reveal a species-specific barrier effect of streetlights on lappet moths whenever the moon was not available as a natural celestial cue. Furthermore, streetlights increased the tortuosity of flight trajectories for both hawk moths and lappet moths. Our results provide the first spatially resolved experimental evidence for the fragmentation of landscapes by streetlights and demonstrate that light pollution affects movement patterns of moths beyond previously assumed extend, potentially affecting their reproductive success and hampering a vital ecosystem service.
Structural analysis and ensemble docking revealed the binding modes of selected progesterone receptor modulators
Authors: Saritha F. , Aiswarya N. , Kumar R. Aswath , Dileep K.V.
Published: October 2022

Uterine fibroids (UF) are benign smooth muscle neoplasm of uterus that have a significant impact on a woman’s quality of life as they perturb hormonal homeostasis resulting in heavy menstrual bleeding, impaired fertility, pregnancy complications and loss. UF can be surgically removed through invasive procedures, but their recurrence rate is often high. Progesterone receptor (PR) has an imperative role in UF management. Mifepristone, ulipristal acetate (UPA) and asoprisnil (ASO) are some promising selective progesterone receptor modulators (SPRMs), acts on PR, but due to their side effects in long term use, they were withdrawn from the market. Hence, there is a dire need for novel, highly efficient with least side effects, therapeutics for the treatment of UF. To contribute towards the drug discovery for UF, we made an extensive structural comparison of reported PR crystal structures, also elucidated the binding modes of four existing SPRMs against human PR through ensemble docking approach. Our studies revealed the presence of 5 highly repeating water molecules that has an important role in ligand binding and structural stability. Our ensemble docking and MD simulation revealed that studied ligands have preferential selectivity towards the specific conformation of PR. It is anticipated that our study will be a useful resource to all the drug discovery scientists who are engaged in the identification of lead molecules against UF.
NRRS: A re-tracing strategy to refine neuron reconstruction
Authors: Li Yiwei , Jiang Shengdian , Liu Lijuan
Published: October 2022

The authors have withdrawn their manuscript because this paper has a conflict of interest. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Inbreeding depression in polyploid species: a meta-analysis
Authors: Clo Josselin , Kolář Filip
Published: October 2022

Whole-genome duplication is a common mutation in eukaryotes with far-reaching phenotypic effects, the resulting morphological and fitness consequences and how they affect the survival of polyploid lineages are intensively studied. Another important factor may also determine the probability of establishment and success of polyploid lineages: inbreeding depression. Inbreeding depression is expected to play an important role in the establishment of neopolyploid lineages, their capacity to colonize new environments, and in the simultaneous evolution of ploidy and other life-history traits such as self-fertilization. Both theoretically and empirically, there is no consensus on the consequences of polyploidy on inbreeding depression. In this meta-analysis, we investigated the effect of polyploidy on the evolution of inbreeding depression, by performing a meta-analysis within angiosperm species. The main results of our study are that the consequences of polyploidy on inbreeding depression are complex and depend on the time since polyploidization. We found that young polyploid lineages have a much lower amount of inbreeding depression than their diploid relatives and their established counterparts. Natural polyploid lineages are intermediate, and have a higher amount of inbreeding depression than synthetic neopolyploids, and a smaller amount than diploids, suggesting that the negative effect of polyploidy on inbreeding depression decrease with time since polyploidization.
Multi range ERK responses shape the proliferative trajectory of single cells following oncogene induced senescence
Authors: Chen Jia-Yun , Hug Clemens , Reyes José , Tian Chengzhe , Gerosa Luca , Fröhlich Fabian , Ponsioen Bas , Snippert Hugo J G , Spencer Sabrina L. , Jambhekar Ashwini , Sorger Peter K. , Lahav Galit
Published: October 2022

Oncogene-induced senescence (OIS) is a phenomenon in which aberrant oncogene expression causes non-transformed cells to enter a non-proliferative state. Cells undergoing OIS display phenotypic heterogeneity, with some cells senescing and others remaining proliferative. The causes of the heterogeneity remain poorly understood. We studied the sources of heterogeneity in the responses of human epithelial cells to oncogenic BRAFV600E expression. We found that a narrow expression range of BRAFV600E generated a wide range of activities of its downstream effector ERK. In population-level and single cell assays, ERK activity displayed a non-monotonic relationship to proliferation, with intermediate ERK activities leading to maximal proliferation. We profiled gene expression across a range of ERK activities over time and characterized four distinct ERK response classes, which we propose act in concert to generate the unique ERK-proliferation response. Altogether, our studies mapped the input-output relationships between ERK activity and proliferation providing important insights into how heterogeneity can be generated during OIS.