bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a certified electronic health record technology platform to screen, test and refer patients with prediabetes
Authors: Kirley Kate , Khan Tamkeen , Aquino Gina , Brown Ameldia , Meier Scott , Chambers Nadene , O’Connell Christopher
Published: December 2021

The objective of this study was to determine if certified electronic health record technology (CEHRT) can be used to identify and refer patients with prediabetes to lifestyle change programs (LCPs) recognized by the National Diabetes Prevention Program (DPP). This pilot utilized a prediabetes registry, patient portal, and clinical decision support to increase referrals. Data from 36 primary care providers showed 4930 patients were eligible for DPP LCP, 293 referrals were generated, compared to 20 referrals in the baseline period, and 116 patients enrolled. Referral to enrollment conversion rates were 41% in the study period and 69% in the post-study 1-year period. CEHRT functionalities can support systematic identification and management of prediabetes. The referral rate increased 7-fold compared to the baseline period, with high referral to enrollment conversion rates. CEHRT coupled with active provider engagement can serve as a tool to identify prediabetes patients and facilitate LCP referrals and enrollment.
Phenotypic and genetic associations between feeding behavior and carcass merit in crossbred growing cattle
Authors: Kelly David N , Sleator Roy D , Murphy Craig P , Conroy Stephen B , Berry Donagh P
Published: December 2021

In growing cattle, the phenotypic and genetic relationships between feeding behavior and both live animal ultrasound measures and subsequent carcass merit are generally poorly characterized. The objective of the current study was to quantify the phenotypic and genetic associations between a plethora of feeding behavior traits with both pre-slaughter ultrasound traits and post-slaughter carcass credentials in crossbred Bos taurus cattle. Carcass data were available on 3,146 young bulls, steers, and heifers, of which 2,795 and 2,445 also had records for pre-slaughter ultrasound muscle depth and intramuscular fat percentage, respectively; a total of 1,548 steers and heifers had information on all of the feeding behavior, ultrasound, and carcass traits. Young bulls were fed concentrates, while steers and heifers were fed a total mixed ration. Feeding behavior traits were defined based on individual feed events or meal events (i.e., individual feed events grouped into meals). Animal linear mixed models were used to estimate (co)variance components. Phenotypic correlations between feeding behavior and both ultrasound and carcass traits were generally weak and not different from zero, although there were phenotypic correlations of 0.40, 0.26, and 0.37 between carcass weight and feeding rate, energy intake per feed event, and energy intake per meal, respectively. Genetically, cattle that had heavier carcass weights, better carcass conformation, or a higher dressing percentage fed for a shorter time per day (genetic correlations [±SE] of −0.46 ± 0.12, −0.39 ± 0.11, and −0.50 ± 0.10, respectively). Genetic correlations of 0.43 ± 0.12 and 0.68 ± 0.13 were estimated between dressing difference (i.e., differential between live weight pre-slaughter and carcass weight) and energy intake per feed event and energy intake per meal, respectively. Neither intramuscular fat percentage measured on live animals nor carcass fat score (i.e., a measure of subcutaneous fat cover of the carcass) was genetically associated with any of the feeding behavior traits. The genetic associations between some feeding behavior traits and both ultrasound and carcass traits herein suggested that indirect responses in the feeding behavior of growing cattle from selection for improved carcass merit would be expected. Such changes in feeding behavior patterns in cattle may be reduced by measuring and including feeding behavior in a multiple-trait selection index alongside carcass traits.
Effects of feeding lubabegron on gas emissions, growth performance, and carcass characteristics of beef cattle housed in small-pen environmentally monitored enclosures during the last 3 mo of the finishing period
Authors: Teeter J Scott , Werth Samantha J , Gruber Sandra L , Kube John C , Hagenmaier Jacob A , Allen Janet B , Herr Cory T , Brown Michael S , Boler Dustin , Dilger Anna C , Zhao Yongjing , Pan Yuee , Mitloehner Frank M
Published: December 2021

The development of technologies that promote environmental stewardship while maintaining or improving the efficiency of food animal production is essential to the sustainability of producing a food supply to meet the demands of a growing population. As such, Elanco (Greenfield, IN) pursued an environmental indication for a selective β-modulator (lubabegron; LUB). LUB was recently approved by the United States Food and Drug Administration (FDA) to be fed to feedlot cattle during the last 14 to 91 d of the feeding period for reductions in gas emissions/kg of unshrunk final BW and HCW. A 4 × 2 factorial arrangement of treatments was used with the factors of dose (0.0, 1.38, 5.5, or 22.0 mg·kg−1 DM basis) and sex (steers or heifers). Three 91-d cycles were conducted (112 cattle/cycle) with each dose × sex combination being represented by a single cattle pen enclosure (CPE; 14 cattle/CPE) resulting in a total of 168 steers and 168 heifers (n = 6 replicates/dose). There were no interactions observed between dose and sex for any variable measured in the study (P ≥ 0.063). Five gases were evaluated for all pens based on CPE concentrations relative to ambient air: NH3, CH4, N2O, H2S, and CO2. Cumulative NH3 gas emissions were reduced by feeding cattle 5.5 and 22.0 mg·kg−1 LUB (P ≤ 0.023) and tended (P = 0.076) to be lower for the cattle fed 1.38 mg·kg−1 LUB compared with the negative controls (CON). The cumulative NH3 gas emission reductions of 960 to 1032 g, coupled with HCW increases (P ≤ 0.019) of 15 to 16 kg for all LUB doses vs. CON, led to reductions in NH3 gas emissions/kg HCW for all three LUB treatments (P ≤ 0.004). Similar to HCW, reductions in NH3 gas emissions/kg of unshrunk final BW were observed for all LUB doses (P ≤ 0.009) and were attributable to both decreases in NH3 gas emissions and numerical increases in BW. Dose had no effect on cumulative emissions or emissions standardized by BW or HCW for the other four gases (P ≥ 0.268). LUB is a novel tool to reduce emissions of NH3 gas per kilogram of unshrunk live BW and hot carcass weight.
Effects of corn processing and cattle size on total tract digestion and energy and nitrogen balance
Authors: Petzel Emily A , Acharya Subash , Zeltwanger Joshua M , Bailey Eric A , Brake Derek W
Published: December 2021

This study used 18 calves (295 ± 29 kg) and 18 yearlings (521 ± 29 kg) fed whole, cracked, or steam-flaked corn (SFC) to evaluate nutrient digestion and energy balance across different types of processed corn and sizes of cattle. Cattle were fed a diet comprised of 75% corn (dry matter [DM]-basis) from whole, cracked, or SFC to 2.5-times maintenance energy requirements. Subsequently, cattle were placed in individual stanchions, and urine and feces were collected together with measures of gas production via indirect calorimetry. Data were analyzed using the MIXED procedure of SAS. There was no interaction between corn processing and cattle size (P ≥ 0.40). Time spent ruminating (min/d) and rumination rate (min/kg DM intake [DMI]) were not affected by corn processing or cattle size. The eating rate (min/kg DMI) was faster (P < 0.01) for yearlings compared with calves. Total tract starch digestion was greatest (P = 0.01) for cattle fed SFC (97.5%), intermediate in cattle fed cracked (92.4%), and least in cattle fed whole corn (89.5%). Dietary digestible energy and metabolizable energy (Mcal/kg DMI) were greater (P ≤ 0.05) for cattle fed SFC compared with cracked or whole. A greater proportion of digestible energy was lost to heat production (P = 0.01) in cattle fed whole corn compared with cracked and tended to be greater (P = 0.08) in cattle fed SFC than cracked. Conversion of digestible energy to metabolizable energy in this study was more closely related to a dynamic model used to estimate metabolizable energy of feeds to dairy cows than to a linear model used to predict metabolizable energy of feeds to beef cattle. If library estimates of net energy for maintenance are correct, then retained energy (Mcal/d) should have been similar between each type of processed corn; however, retained energy was greater (P < 0.01) for cattle fed cracked compared with whole corn and tended to be greater (P = 0.06) compared with SFC. Yet, observed amounts of net energy based on measures of retained energy were not different (P ≥ 0.60) between cracked and SFC. Nitrogen balance was not affected (P ≥ 0.30) by corn processing or cattle size, although cattle fed cracked had numerically greater (P ≤ 035) N retention. These data indicate that physical processing of corn provides greater net energy to cattle in comparison to whole corn.
Ectopic Implantation Salvage of the Left Thumb to Reconstruct the Right Thumb After Electrical Injury: A Case Report
Authors: Du Weili , Jiang Huihao , Cheng Lin , Zhang Ying , Qin Fengjun , Shen Yuming
Published: December 2021

The incidence rate of electrical injury has remained stable, while the absolute case number has increased. Amputations, erosions, occlusions, and delayed blood vessel rupture are the common complications. Ectopic implantation salvage has been performed widely in mechanical trauma patients, to preserve viable or possibly viable tissues and organ, without application in the electrical injury patients to the best of our knowledge. Here, we present a case report involving ectopic implantation salvage of the left thumb before contralateral transplantation to the right hand after high-voltage electrical injury. The patient’s left thumb remained viable despite necrosis of the left forearm at 3 weeks postinjury. After debridement, we implanted the left thumb to his thigh where it was anastomosed to the lateral circumflex femoral artery’s descending branch and great saphenous vein. We replanted the left thumb on the right hand with fixation 6 weeks later. The reassembled right hand remained well-circulated 11 months postreconstruction. We believe this case supports broadening the indication for ectopic implantation salvage surgeries to patients who sustain electrical injuries.
The Editors of Scientific Journals in Dentistry in Nazi Germany and after 1945: A Sociodemographic Study
Authors: Bergmann Cynthia , Westemeier Jens , Gross Dominik
Published: December 2021

This socio-demographic study examines the effects of the Nazification of the professional press in the Third Reich using the example of the dental press organs. Three subgroups were examined: (1) dental editors who lost their positions after Hitler assumed power; (2) editors who were newly appointed or confirmed in their positions during the Third Reich; and (3) editors who were recruited for these positions in the post-war period.

The study was based on archival sources, contemporary registers, and dental journals from 1932-1949. These sources were supplemented by available secondary literature. A total of 34 editors were identified and their biographies reconstructed. Several of the editors appointed during the Nazi regime were able take up their positions again after 1945. Overall, the majority of editors appointed between 1945-1950 were former party members; in contrast, not a single Nazi victim was appointed to a position of this kind. We conclude in this article that denazification had no consequences for the specialist dental press. On the contrary, dentists who had benefited professionally from the Nazi regime during the Third Reich stood a good chance of furthering their careers after 1945.
Detection of Orientia tsutsugamushi in Novel Trombiculid Mite Species in Northern Tamil Nadu, India: Use of Targeting the Multicopy traD Gene
Authors: Prakash John Antony Jude , Kamarasu Kannan , Samuel P Philip , Govindarajan Renu , Govindasamy Punitha , Johnson Liji Anna , Ramalingam P , Nirmalson J , Seran K C
Published: December 2021

Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it might be a potential vector of scrub typhus in an endemic area. Over a period of 20 mo, 85 rats were trapped, 57 had chiggers that were identified by standard morphometric techniques. The chigger pools were assessed by performing PCR assays targeting fragments of the single-copy genes 56 kDa type-specific antigen gene (TSA56) by nested PCR and the 47 kDa (htrA) quantitative real-time PCR (qPCR). The novel traD SYBR green assay that detects a multicopy gene was also performed. In total, 27 chigger pools were positive by traD qPCR, of which only 7 were positive by 47 kDa qPCR and in 3 of these, 56 kDa gene was amplified by nested PCR. Orientia tsutsugamushi-specific DNA was detected in Ascoschoengastia spp., Schoengastiella ligula, Leptotrombidium rajasthanense, Leptotrombidium deliense, and Leptotrombidium jayawickremei chigger pools. Therefore, they could be potential vectors of scrub typhus in Southern India. The three 56 kDa sequences belonged to TA716 genotype and Kato genogroup. Further studies are needed to confirm these chigger species as scrub typhus vectors in Northern Tamil Nadu.
Investigating the lower extremity–related anaerobic exercise capacity and functional status in adult patients with familial Mediterranean fever
Authors: Acar Merve Eylul , Bayraktar Deniz , Gucenmez Sercan , Sarac Devrim Can , Buker Nurullah , Kocak Umut Ziya , Solmaz Dilek , Akar Servet
Published: December 2021

Objectives

No studies examined the lower extremity–related anaerobic exercise capacity or functional status in adult patients with FMF.

Methods

Twenty-four patients with FMF (12 males) and 24 age–sex-matched healthy controls (13 males) were included in the study. Lower extremity–related anaerobic exercise capacity was assessed by using Wingate Anaerobic Test. Lower extremity–related functional status was examined by using 9-Step Stair Climb Test, 10-Repetition Chair Stand Test, and Six-Minute Walking Distance. Muscle strength of hip flexors, hip extensors, knee flexors, and knee extensors were evaluated by using a hand-held dynamometer.

Results

Patients with FMF had significantly poorer results in all anaerobic exercise capacity parameters and functional status assessments (P < 0.05), except muscle strength measurements (P > 0.05). Both average and peak anaerobic exercise capacities correlated significantly with all muscle strength measurements, 9-Step Stair Climb Test, 10-Repetition Chair Stand Test times, and Six-Minute Walk Distances (P < 0.05) in patients with FMF.

Conclusion

Lower extremity–related anaerobic exercise capacity and functional status seem to be diminished in adult patients with FMF. Evaluating these parameters may be beneficial for planning more appropriate and individualized treatment regimens such as patient education and exercise counselling for patients with FMF.
Audiological involvement in patients with systemic sclerosis
Authors: Turan Kubra , Yayla Mucteba Enes , Arslan Murat , Tokgoz Yilmaz Suna , Okatan Ercan , Turgay Murat , Meco Cem
Published: December 2021

Objectives

The aim of the present study was to evaluate hearing loss in patients diagnosed with systemic sclerosis (SSc) and to investigate the relation between hearing loss, subtypes of the disease, its duration and clinical findings, and antibody positivity.

Methods

The study included 47 patients with SSc and 44 healthy controls. Audiometric, tympanometric, and otoacoustic emission measurements were applied to both groups.

Results

The evaluation of the participants medical history showed that among the patients with SSc, 19.1% experienced ear fullness, 27.7% experienced vertigo, and 36.2% experienced tinnitus. Hearing loss was detected in 23.4% of the patients with SSc. The corresponding result was 4.3% in the control group with a statistically significant difference (p = 0.001). Transient-evoked otoacoustic emission amplitude values were significantly lower in the patients’ both ears with SSc than the control group (p < 0.005). Duration of disease was significantly longer, and diffusing capacity of the lungs for carbon monoxide values were significantly higher in the patients with SSc and sensorineural hearing loss.

Conclusions

The present study found that the incidence of hearing loss was significantly higher in the study group than in the healthy control group. In addition to other organ involvements, cochlear involvement occurs in these patients, and further studies are required.
Mitochondrial Fission Complex Is Required for Long-Term Heat Tolerance of Arabidopsis
Authors: Tsukimoto Ryo , Isono Kazuho , Kajino Takuma , Iuchi Satoshi , Shinozawa Akihisa , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: December 2021

Plants are often exposed not only to short-term (S) heat stress but also to long-term (L) heat stress over several consecutive days. A few Arabidopsis mutants defective in L-heat tolerance have been identified, but the molecular mechanisms involved are less well understood than those involved in S-heat tolerance. To elucidate the mechanisms, we isolated the new sensitive to long-term heat5 (sloh5) mutant from EMS-mutagenized seeds of L-heat-tolerant Col-0. The sloh5 mutant was hypersensitive to L-heat but not to S-heat, osmo-shock, salt-shock or oxidative stress. The causal gene, SLOH5, is identical to elongatedmitochondria1 (ELM1), which plays an important role in mitochondrial fission in conjunction with dynamin-related proteins DRP3A and DRP3B. Transcript levels of ELM1, DRP3A and DRP3B were time-dependently increased by L-heat stress, and drp3a drp3b double mutants were hypersensitive to L-heat stress. The sloh5 mutant contained massively elongated mitochondria. L-heat stress caused mitochondrial dysfunction and cell death in sloh5. Furthermore, WT plants treated with a mitochondrial myosin ATPase inhibitor were hypersensitive to L-heat stress. These findings suggest that mitochondrial fission and function are important in L-heat tolerance of Arabidopsis.
Detecting Fibered Strongly Quasi-Positive Links
Authors: Cavallo Alberto
Published: December 2021

We prove that an n-component fibered link L in S3 is strongly quasi-positive if and only if $\tau(L)=g_3(L)+n-1$, where $g_3(L)$ denotes the Seifert genus and τ is the Ozsváth–Szabó concordance invariant. We also provide a table which contains a list of some fibered prime links with at most 9 crossings; and we explicitly determine the ones that are strongly quasi-positive and their maximal self-linking number.
Opportunities for theory-informed decision science in cancer control
Authors: Gillman Arielle S , Ferrer Rebecca A
Published: December 2021

Cancer prevention and control involves navigation of complex clinical decisions, often laden with uncertainty and/or intricate interpersonal dynamics, which have implications for both physical health and quality of life. Cancer decision-making research in recent decades has primarily focused on working to improve the quality of decisions by providing patients with detailed information about their choices and through an increased emphasis in medicine on the importance of shared decision making. This emphasis is reflective of a model of decision making that emphasizes knowledge, options, and deliberative synthesis of information as primary to decision making; yet, decades of research in psychology, decision science, and behavioral economics have taught us that our decisions are not influenced only by our objective knowledge of facts, but by our emotions, by the influence of others, and by biased cognitive processes. We present a conceptual framework for a future of research in decision science and cancer that is informed by decision science theories. Our framework incorporates greater recognition of the interpersonal dynamics of shared decision making, including the biases (including cognitive heuristics and race-based bias) that may affect multiple actors in the decision-making process, and emphasizes study of the interaction between deliberative and affective psychological processes as they relate to decision making. This work should be conducted with an eye toward informing efforts to improve decision making across the cancer care continuum, through interventions that are also informed by theory.
Cellular and Molecular Pathways Underlying the Nephrotoxicity of Gadolinium
Authors: Reis Sousa Nícia , Rocha Susana , Santos-Silva Alice , Coimbra Susana , Valente Maria João
Published: December 2021

Mounting evidence on the short- and long-term adverse effects associated with gadolinium [Gd (III)]-based contrast agents used in magnetic resonance imaging have emerged in the past 3 decades. Safety issues arise from the release of Gd (III) from chelates and its deposition in tissues, which is exacerbated in patients with renal disease, because the kidney is the major excretion organ of most of these agents. This study aimed at unveiling the cellular and molecular mechanisms of nephrotoxicity of Gd (III), using an in vitro model of human proximal tubular cells (HK-2 cell line). Cell viability declined in a concentration- and time-dependent manner after exposure to GdCl3·6H2O. The estimated inhibitory concentrations (ICs) eliciting 1%–50% of cell death, after 24 h of exposure, ranged from 3.4 to 340.5 µM. At toxic concentrations, exposure to Gd (III) led to disruption of the oxidative status, mitochondrial dysfunction, cell death by apoptosis, switching to necrosis at higher levels, and autophagic activation. Disturbance of the lipid metabolism was already observed at low-toxicity ICs, with accumulation of lipid droplets, and upregulation of genes related to both lipogenesis and lipolysis. Gd (III)-exposure, even at the subtoxic IC01, increased the expression of modulators of various signaling pathways involved in the development and progression of renal disease, including inflammation, hypoxia, and fibrosis. Our results give new insights into the mechanisms underlying the nephrotoxic potential of Gd (III) and highlight the need to further clarify the risks versus benefits of the Gd (III)-based contrast agents currently in use.
Reappraisal and new material of the holotype ofDraconyx loureiroi(Ornithischia: Iguanodontia) provide insights on thetempoandmodoof evolution of thumb-spiked dinosaurs
Authors: Rotatori Filippo Maria , Moreno-Azanza Miguel , Mateus Octávio
Published: December 2021

The Upper Jurassic Lourinhã Formation is well known for its rich assemblage of fossil vertebrates. In this formation, ornithopod dinosaurs are represented by two iguanodontian species, Eousdryosaurus nanohallucis and Draconyx loureiroi. We recently became aware of unreported material belonging to the holotype of Draconyx loureiroi, consisting of partially articulated manual elements. We here re-describe the holotype specimen ML 357, including the newly discovered material. The specimen was subjected to CT-scanning and its surface data used to assess anatomical characters. Linear measurements of metatarsal III were used to estimate the body length of the specimen. The Draconyx loureiroi holotype was included in two datasets and analysed with maximum parsimony and Bayesian inference approaches to estimate evolutionary rates among Iguanodontia. We present evidence that Draconyx loureiroi is a valid taxon nested in Styracosterna and is clearly diagnosable by a unique combination of characters. Both maximum parsimony and Bayesian inference indicate high evolutionary rates across the Jurassic/Cretaceous transition for the base of Iguanodontia. Length estimation suggests that Draconyx loureiroi was a relatively small, bipedal and possibly cursorial animal. Given its basal phyletic position, we interpret this bauplan was the ancestral condition for Styracosterna, that only later in the Cretaceous evolved into giant quadrupedal forms.
A Review of Venous Thromboembolism Risk Assessment and Prophylaxis in Plastic Surgery
Authors: Agrawal Nikhil A. , Hillier Kirsty , Kumar Riten , Izaddoost Shayan A. , Rohrich Rod J.
Published: December 2021

Background:

Venous thromboembolism is a significant cause of postoperative death and morbidity. While prophylactic and treatment regimens exist, they usually come with some risk of clinically relevant bleeding and, thus, must be considered carefully for each individual patient.

Methods:

This special topic article represents a review of current evidence regarding venous thromboembolism risk, biology, and prevention in plastic surgery patients. The specific types and duration of available prophylaxis are also reviewed. The balance of venous thromboembolism risk must be weighed against the risk of hemorrhage.

Results:

Though alternatives exist, the most validated risk assessment tool is the 2005 modification of the Caprini Risk Assessment Model. Controversies remain regarding recommendations for outpatient and low risk cosmetic patients. The authors additionally make recommendations for high-risk patients regarding the use of tranexamic acid, estrogen therapy, anesthesia, and prophylaxis regimens.

Conclusion:

Our profession has made great strides in understanding the science behind venous thromboembolism, risk stratification for patients, and prophylactic regimens; yet, continued studies and definitive data are needed.
Accelerating access and scale-up of optimized antiretroviral therapy in low-income and middle-income countries: results of a coordinated end-to-end approach
Authors: Harris Emily Lark , Blumer Katherine , Perez Casas Carmen , Ferris Danielle , Amole Carolyn , Doherty Meg , Auton Martin
Published: December 2021

The global HIV community invested in multiple, high-profile partnerships and shepherded unprecedented political support to expedite the transition to dolutegravir (DTG)-based regimens. The goal? To accelerate access to simpler, safer, more robust, and more affordable HIV treatment by harnessing the collective power of scientists, regulators, drug companies, donors, implementers, advocates, and people with HIV (PWH). The inspiration? End-to-end approaches to introducing new products that mitigate risk and encourage early planning and resource allocation for all aspects of product introduction and preparation for scale-up. This approach of planning with the ‘end-in-mind’ – and the belief that this end-to-end mindset can facilitate healthy markets, catalyze the application of new health technologies, and accelerate the development of improved products – is increasingly being applied across HIV prevention, care, and treatment (e.g. for biomedical prevention), and across health sectors (e.g. in maternal and child health, food security and water, and sanitation). This review of antiretroviral treatment (ART) optimization efforts from 2015 through 2020 discusses what worked, what is next, and how the learnings from HIV treatment can inform the broader global health community looking for innovative partnership models to accelerate adoption and enable scale-up of promising new products and programs.
Adherence, resistance, and viral suppression on dolutegravir in sub-Saharan Africa: implications for the TLD era
Authors: McCluskey Suzanne M. , Pepperrell Toby , Hill Andrew , Venter Willem D.F. , Gupta Ravindra K. , Siedner Mark J.
Published: December 2021

Dolutegravir (DTG) is now a component of preferred first-line antiretroviral therapy (ART) worldwide. ADVANCE and NAMSAL were two landmark clinical trials conducted exclusively in sub-Saharan Africa, which studied the effectiveness of DTG-based first-line regimens for ART-naive individuals. In this review, we examine the data from these studies to consider the contributions of adherence and HIV drug resistance to treatment failure on DTG-based ART, as compared with efavirenz (EFV)-based ART, which has a lower genetic barrier to resistance. We also discuss the implications of virologic failure on DTG and consolidate currently available data to conclude with recommendations for virologic monitoring on DTG-based ART.
Weight gain stopping/switch rules for antiretroviral clinical trials
Authors: Venter W.D. Francois , Sokhela Simiso , Calmy Alexandra , Mkhondwane Luckyboy , Bosch Bronwyn , Chandiwana Nomathemba , Hill Andrew , Sekwese Kenly , Mashabane Nkuli , Pozniak Anton , Khoo Saye , Ali Mohammed , Delaporte Eric , Lalla-Edwards Samanta , Clayden Polly , Marconi Vincent C. , Siedner Mark J. , Boffito Marta , Serenata Celicia , Carman Mary , Collins Simon
Published: December 2021

Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens’ potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when “too much” weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.
Impact of Donepezil and Memantine on Behavioral and Psychological Symptoms of Alzheimer Disease: Six-month Open-label Study
Authors: Bago Rožanković Petra , Rožanković Marjan , Badžak Jasna , Stojić Maristela , Šušak Sporiš Ivana
Published: December 2021

Background:

Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the treatment of moderate AD.

Objective:

To evaluate the effects of donepezil and memantine in relieving BPSD in individuals with moderate AD.

Method:

We conducted a prospective, randomized, 6-month clinical trial involving 85 individuals with moderate AD divided into two groups: group 1 (n = 42) was treated with donepezil; group 2 (n = 43) was treated with memantine. We used the Neuropsychiatric Inventory (NPI) to assess the prevalence and severity of BPSD at baseline and after 6 months of treatment with donepezil or memantine.

Results:

The two groups’ baseline characteristics, including age, sex, mean length of education, and disease duration, were comparable, as were their baseline Mini-Mental State Examination scores. The NPI Total score improved from baseline to month 6 in both groups (P < 0.0001). Analyses of the NPI subdomains revealed that both donepezil treatment and memantine treatment produced statistically significant improvement in all of the NPI domains except euphoria and apathy, for which no improvement was observed after memantine treatment. Both treatments were well tolerated, with mostly mild and transient adverse effects.

Conclusion:

Specific drugs for AD, including donepezil and memantine, may be effective in treating BPSD in individuals with moderate AD, with a favorable safety profile.
Lymph node swelling combined with temporary effector T cell retention aids T cell response in a model of adaptive immunity
Authors: Johnson Sarah C. , Frattolin Jennifer , Edgar Lowell T. , Jafarnejad Mohammad , Moore Jr James E.
Published: December 2021

Swelling of lymph nodes (LNs) is commonly observed during the adaptive immune response, yet the impact on T cell (TC) trafficking and subsequent immune response is not well known. To better understand the effect of macro-scale alterations, we developed an agent-based model of the LN paracortex, describing the TC proliferative response to antigen-presenting dendritic cells alongside inflammation-driven and swelling-induced changes in TC recruitment and egress, while also incorporating regulation of the expression of egress-modulating TC receptor sphingosine-1-phosphate receptor-1. Analysis of the effector TC response under varying swelling conditions showed that swelling consistently aided TC activation. However, subsequent effector CD8+TC production was reduced in scenarios where swelling occurred too early in the TC proliferative phase or when TC cognate frequency was low due to increased opportunity for TC exit. Temporarily extending retention of newly differentiated effector TCs, mediated by sphingosine-1-phosphate receptor-1 expression, mitigated any negative effects of swelling by allowing facilitation of activation to outweigh increased access to exit areas. These results suggest that targeting temporary effector TC retention and egress associated with swelling offers new ways to modulate effector TC responses in, for example, immuno-suppressed patients and to optimize of vaccine design.
Diffusion of water in palm leaf materials
Authors: Mohanty Debapriya Pinaki , Udupa Anirudh , Viswanathan Koushik , Gilpin Christopher J. , Chandrasekar Srinivasan , Dayananda Mysore
Published: December 2021

Diffusion of water into plant materials is known to decrease their mechanical strength and stiffness but improve formability. Here, we characterize water diffusion through areca palm leaf-sheath—a model plant material, with hierarchical structure, used in eco-friendly foodware. The diffusion process is studied using mass gain measurements andin situimaging of water transport. By treating the areca sheath as homogeneous ensemble, and incorporating effects of material swelling due­ to water absorption, a factor typically neglected in prior studies, the diffusion coefficientDwfor water is estimated as (6.5 ± 2.2) × 10−4mm2s−1. It is shown that neglecting the swelling results in gross underestimation ofDw. Microstructural effects (e.g. fibre, matrix) on the diffusion are characterized usingin situimaging of the water transport at high resolution. The observations show that the water diffuses an order of magnitude faster in the matrix (8.63 × 10−4mm2s−1) than in the fibres (7.19 × 10−5mm2s−1). This non-uniformity is also reflected in the swelling-induced strain in the leaf, mapped by image correlation. Lastly, we vary salt concentration by controlled additions of NaCl and note a non-monotonic dependence of the diffusion on concentration. Implications of the results for improving foodware manufacturing processes and product life are discussed.
Functional diversity increases the efficacy of phage combinations
Authors: Wright Rosanna C. T. , Friman Ville-Petri , Smith Margaret C. M. , Brockhurst Michael A.
Published: December 2021

Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from one to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximized at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.
Saccade dynamics in the recovery phase of abducens nerve palsy
Authors: Kemanetzoglou E , Chatzistefanou KI , Smyrnis N , Kararizou E , Anagnostou E
Published: December 2021

INTRODUCTION

Despite the fact that abducens nerve palsy (ANP) is the most common ocular motor palsy, the literature on the respective saccade dynamics, both in the paretic (PE) and non-paretic eye (nPE), is scarce.

AIMS AND METHODOLOGY

The aim of this study was to examine the maximum velocity, duration and accuracy of horizontal saccades, in individuals with unilateral ANP, and to compare them with normal controls. Binocular horizontal eye movements were recorded at 5°, 10° and 15°, using an infrared corneal reflection device from 21 adults with microvascular unilateral ANP during the acute and the chronic phase of the palsy, as well as 18 healthy adults. Non-parametric tests were used for statistical comparisons.

RESULTS

The PE, when compared to the nPE, presents a slightly lower saccadic amplitude and velocity/amplitude ratio and a higher duration/amplitude ratio. The nPE, compared to the healthy eye (HE) of the control group, showed consistently amplitude gain >1 while the velocity/amplitude ratio did not differ in either session. The duration/amplitude ratio tended to be higher in the nPE. The prism dioptres of the PE did not appear to correlate with any parameter tested (amplitude gain, velocity/amplitude ratio, duration/amplitude ratio) of the open nPE, but the amplitude ratio was statistically lower during the first session when the nPE was kept covered and the duration/amplitude ratio decreased significantly.

CONCLUSIONS

One of the main findings of the study is the increase in saccade duration during adaptation of ANP. Specifically, the nPE performed orthometric saccades with a longer duration than healthy controls. Given that the motor command reaches the ocular muscles by neural discharges with a “pulse-step” pattern, any adaptation reflects in a change of this pattern. Cerebellar learning leads to an increase in the pulse width of the neural discharge. This idiosyncratic response may be related to plastic changes in central structures that serve learning processes such as the cerebellum. Further research could provide more insight into the cerebellar plastic processes involved in the saccadic adaptation.
Use of heat-not-burn tobacco products, moderate alcohol drinking, and anti-SARS-CoV-2 IgG antibody titers after BNT162b2 vaccination among Japanese healthcare workers
Authors: Yamamoto Shohei , Tanaka Akihito , Ohmagari Norio , Yamaguchi Koushi , Ishitsuka Kazue , Morisaki Naho , Kojima Masayo , Nishikimi Akihiko , Tokuda Haruhiko , Inoue Manami , Tanaka Shiori , Umezawa Jun , Okubo Ryo , Nishimura Kunihiro , Konishi Maki , Miyo Kengo , Mizoue Tetsuya
Published: December 2021

Background

The effect of heat-not-burn (HNB) tobacco product use and moderate alcohol drinking on immunogenicity to coronavirus disease (COVID-19) vaccines remain elusive. This study aimed to examine the association of tobacco product use and alcohol consumption with anti-SARS-CoV-2 spike IgG antibody titers after the BNT162b2 vaccine.

Methods

Participants were 3,457 fully vaccinated healthcare workers in the 4 national centers for advanced medical and research in Japan. Smoking status and alcohol consumption were assessed via a questionnaire, and anti-SARS-CoV-2 spike IgG titers were measured by chemiluminescent enzyme immunoassay using serum collected on the median of 64 days after the second vaccination. Multilevel linear regression models were used to estimate the geometric mean titers (GMT) and the ratios of means (RoM) between groups.

Results

Of vaccinated participants, 99.5% (3,440/3,457) were seropositive. Compared with never-smokers (GMT=119), IgG antibody titers were significantly lower among HNB tobacco users (including those who also smoked cigarettes) (GMT=105; RoM=0.88 [95%CI: 0.78–0.99]) and exclusive cigarettes smokers (GMT=96; RoM=0.81 [95%CI: 0.71–0.92]). Compared with non-drinkers of alcohol (GMT=123), alcohol drinkers consuming <1 go/day (GMT=114; RoM=0.93 [95%CI: 0.88–0.98]), 1–1.9 go/day (GMT=105; RoM=0.85 [95%CI: 0.79–0.93]), and ≥2 go/day (GMT=101; RoM=0.82 [95%CI: 0.72–0.94]) had significantly lower antibody titers (P for trend<0.01). Spline analysis showed a large reduction of antibody until around 1 go/day of alcohol consumption, and then they gradually decreased.

Conclusions

Results suggest that in addition to conventional cigarette smoking and heavy alcohol drinking, use of HNB tobacco products and moderate alcohol drinking may be predictors of lower immunological response to COVID-19 vaccine.

Key Messages

Epidemiological evidence regarding the association of smoking status and alcohol drinking with COVID-19 vaccine-induced antibody levels is scarce.

Users of heat-not-burn (HNB) tobacco products, as well as cigarettes smokers, had lower antibody titers than never-smokers.

Not only high-dose but moderate-dose alcohol intake was also associated with decreased vaccine-induced antibody levels.

HNB tobacco product use and moderate alcohol drinking may be modifiers of COVID-19 vaccine-induced immunogenicity.
A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD
Authors: Wang Xiaofei , Hu Ao , Chen Xiangyu , Zhang Yixin , Yu Fei , Yue Shuai , Li Arong , Zhang Junsong , Pan Zhiwei , Yang Yang , Lin Yao , Gao Leiqiong , Zhou Jing , Zhao Jing , Li Fang , Shi Yaling , Huang Feng , Yang Xiaofan , Peng Yi , Tu Luoyang , Zhang Huan , Zheng Huanying , He Jun , Zhang Hui , Xu Lifan , Huang QizhAo , Zhu Yongqun , Deng Kai , Ye Lilin
Published: December 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.
Graph Transformer for drug response prediction
Authors: Chu Thang , Nguyen Tuan
Published: December 2021

Background

Previous models have shown that learning drug features from their graph representation is more efficient than learning from their strings or numeric representations. Furthermore, integrating multi-omics data of cell lines increases the performance of drug response prediction. However, these models showed drawbacks in extracting drug features from graph representation and incorporating redundancy information from multi-omics data. This paper proposes a deep learning model, GraTransDRP, to better drug representation and reduce information redundancy. First, the Graph transformer was utilized to extract the drug representation more efficiently. Next, Convolutional neural networks were used to learn the mutation, meth, and transcriptomics features. However, the dimension of transcriptomics features is up to 17737. Therefore, KernelPCA was applied to transcriptomics features to reduce the dimension and transform them into a dense presentation before putting them through the CNN model. Finally, drug and omics features were combined to predict a response value by a fully connected network. Experimental results show that our model outperforms some state-of-the-art methods, including GraphDRP, GraOmicDRP.

Availability of data and materials

https://github.com/chuducthang77/GraTransDRP.
HiC-GNN: A Generalizable Model for 3D Chromosome Reconstruction Using Graph Convolutional Neural Networks
Authors: Van Hovenga  , Oluwadare Oluwatosin , Kalita Jugal
Published: December 2021

Chromosome conformation capture (3C) is a method of measuring chromosome topology in terms of loci interaction. The Hi-C method is a derivative of 3C that allows for genome wide quantification of chromosome interaction. From such interaction data, it is possible to infer the three-dimensional (3D) structure of the underlying chromosome. In this paper, we use a node embedding algorithm and a graph neural network to predict the 3D coordinates of each genomic loci from the corresponding Hi-C contact data. Unlike other chromosome structure prediction methods, our method can generalize a single model across Hi-C resolutions, multiple restriction enzymes, and multiple cell populations while maintaining reconstruction accuracy. We derive these results using three separate Hi-C data sets from the GM12878, GM06990, and K562 cell lines. We also compare the reconstruction accuracy of our method to four other existing methods and show that our method yields superior performance. Our algorithm outperforms the state-of-the-art methods in the accuracy of prediction and introduces a novel method for 3D structure prediction from Hi-C data.

Author Summary

We developed a novel method, HiC-GNN, for predicting the three-dimensional structures of chromosomes from Hi-C data. HiC-GNN is unique from other methods for chromosome structure prediction in that it learns in an eager setting rather than a lazy setting. Thus, the models learned by HiC-GNN can be generalized to unseen data. To the authors’ knowledge, this generalizing capability is not present in any existing methods. We show that this generalization is robust to input resolution, restriction enzyme, and contact sparsity. We also show that our method outperforms existing methods using both generalized and non-generalized models. Moreover, we also show that our method is more robust to contact variance than the compared methods.

Availability

All our source codes and data are available at https://github.com/OluwadareLab/HiC-GNN, and is made available as a containerized application that can be run on any platform.