bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Sample Multivariable Mendelian Randomization Analysis Using R
Authors: Rasooly Danielle , Peloso Gina M.
Published: December 2021

Mendelian randomization is a framework that uses measured variation in genes for assessing and estimating the causal effect of an exposure on an outcome. Multivariable Mendelian randomization is an extension that can assess the causal effect of multiple exposures on an outcome, and can be advantageous when considering a set (>1) of potentially correlated candidate risk factors in evaluating the causal effect of each on a health outcome, accounting for measured pleiotropy. This can be seen, for example, in determining the causal effects of lipids and cholesterol on type 2 diabetes risk, where the correlated risk factors share genetic predictors. Similar to univariate Mendelian randomization, multivariable Mendelian randomization can be conducted using two‐sample summary‐level data where the gene‐exposure and gene‐outcome associations are derived from separate samples from the same underlying population. Here, we present a protocol for conducting a two‐sample multivariable Mendelian randomization study using the ‘MVMR’ package in R and summary‐level genetic data. We also provide a protocol for searching and obtaining instruments using available data sources in the ‘MRInstruments’ R package. Finally, we provide general guidelines and discuss the utility of performing a multivariable Mendelian randomization analysis for simultaneously assessing causality of multiple exposures. © 2021 Wiley Periodicals LLC.

Basic Protocol: Performing a two‐sample multivariable Mendelian randomization analysis using the ‘MVMR’ package in R and summarized genetic data

Support Protocol 1: Installing the ‘MVMR’ R package

Support Protocol 2: Obtaining instruments from the ‘MRInstruments’ R package
Subthreshold reference circuit with curvature compensation based on the channel length modulation of MOS devices
Authors: Aminzadeh Hamed
Published: December 2021

A subthreshold nano‐power voltage and current reference with high‐order temperature compensation is proposed by taking advantage of the channel length modulation of MOS devices. Curvature compensation is implemented by providing proper compensating drain‐source voltages for the core devices of a first‐order CMOS reference such that the output nonlinear temperature factors can be compensated over a wide temperature range. In‐depth mathematical analysis is carried out to model the temperature dependency of the reference signals before and after compensation. As part of the analysis, Taylor expansion of the threshold voltage of MOS devices has been evaluated in a generalized fashion, enabling to clarify the complicated relationship between the high‐order temperature‐related terms of the output and design parameters. Simulated in a standard 0.18‐μm CMOS process, the minimum supply voltage of a proof‐of‐concept design is 1.0 V, providing 345 mV voltage reference with minimum temperature coefficient (TC) of 2.0 ppm/°C across the range of –40–140°C. The active area is 0.45 mm2 with around 200 nA current consumption. The DC line regulation is 0.23%/V, and the power supply rejection ratio (PSRR) is −63 dB at 10 Hz.
EMT‐cancer cells‐derived exosomal miR‐27b‐3p promotes circulating tumour cells‐mediated metastasis by modulating vascular permeability in colorectal cancer
Authors: Dou Rongzhang , Liu Keshu , Yang Chaogang , Zheng Jinsen , Shi Dongdong , Lin Xiaobin , Wei Chen , Zhang Chunxiao , Fang Yan , Huang Sihao , Song Jialin , Wang Shuyi , Xiong Bin
Published: December 2021

Background

Metastasis is the main cause of death in colorectal cancer (CRC). Circulating tumour cells (CTCs) are regarded as the precursor cells of metastasis. The CTCs, which underwent epithelial‐mesenchymal transition (EMT), are associated with metastasis and responsible for poor prognosis. EMT cancer cells modulate endothelial permeability in the invasive front and facilitate cancer cell intravasation, resulting in CTCs‐mediated distant metastasis. Exosomes derived from cancer cells are key mediators of cancer‐host intercommunication. However, the mechanism by which EMT‐tumour cells‐derived exosomes modulate vascular permeability and promote CTCs generation has remained unclear.

Methods

Exosomes isolation and purification were conducted by ultra‐centrifugation. Exosomal miRNA was identified by sequencing followed by quantitative PCR. In vitro co‐culture assay experiments were conducted to evaluate the effect of exosomal miR‐27b‐3p on the permeability of blood vessel endothelium. Dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were performed to investigate the underlying mechanism by which miR‐27b‐3p is packaged into exosomes. A mouse model was established to determine the role of exosomal miR‐27b‐3p in blood vessel permeability modulation in vivo.

Results

We found that EMT‐CRC cells attenuate the blood vessel barrier by transferring miR‐27b‐3p to human umbilical vein endothelial cells (HUVECs) in exosomes. Mechanically, miR‐27b‐3p atteuated the expression of vascular endothelial cadherin (VE‐Cad) and p120 at the post‐transcriptional level by binding to 3′‐untranslated region of VE‐Cad and p120 directly. The packaging of miR‐27b‐3p into exosomes was induced by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which activated by STAT3. Clinically, miR‐27b‐3p up‐regulated in CRC tissues. Plasma exosomal miR‐27b‐3p was positively correlated with malignant progression and CTC count in CRC patients. Our study reveals a novel mechanism by which EMT‐CRC cells promote metastasis, increasing blood vessel permeability and facilitating the generation of CTCs.

Conclusion

Exosomal miR‐27b‐3p secreted by EMT‐CRC cells increases blood vessel permeability and facilitates the generation of CTCs. Exosomal miR‐27b‐3p may become a promising biomarker for CRC metastasis.
Capture vulnerability of sea turtles on recreational fishing piers
Authors: Lamont Margaret M. , Mollenhauer Robert , Foley Allen M.
Published: December 2021

Capture vulnerability of commercial and recreational fishes has been associated with behavioral, morphological, and life‐history traits; however, relationships with non‐target species, such as sea turtles, have not been adequately studied. We examined species composition, timing of captures, morphological variables including body size and head width, and body condition of sea turtles captured from a recreational fishing pier in the northern Gulf of Mexico and of sea turtles captured in the waters adjacent to the pier. From 2014 to 2019, 148 net captures and 112 pier captures of three sea turtle species were documented. Green turtles were captured most frequently in the net and on the pier. Turtles captured from the pier were larger than those captured in the net. There was no difference in head width between net‐caught and pier‐caught turtles; however, small sample sizes limited those comparisons. The body condition index was lower for pier‐caught than net‐caught Kemp’;s ridleys but did not differ with green turtles or loggerheads. Differences were also observed in the timing of capture on the pier as compared to in the net. Finally, the relationship between size, body condition, and pier‐capture vulnerability suggests these are complex interactions. Mortality of sea turtles captured from fishing piers could be selecting against bolder individuals, which may result in changes in sea turtle population demographics over a long time period.
DNA metabarcoding reveals introduced species predominate in the diet of a threatened endemic omnivore, Telfair’s skink (Leiolopisma telfairii)
Authors: Tercel Maximillian P. T. G. , Moorhouse‐Gann Rosemary J. , Cuff Jordan P. , Drake Lorna E. , Cole Nik C. , Goder Martine , Mootoocurpen Rouben , Symondson William O. C.
Published: December 2021

Introduced species can exert disproportionately negative effects on island ecosystems, but their potential role as food for native consumers is poorly studied. Telfair's skinks are endemic omnivores living on Round Island, Mauritius, a globally significant site of biodiversity conservation. We aimed to determine the dietary diversity and key trophic interactions of Telfair's skinks, whether introduced species are frequently consumed, and if diet composition changes seasonally between male and female skinks. We used DNA metabarcoding of skink fecal samples to identify animals (COI) and plants (ITS2) consumed by skinks. There were 389 dietary presence counts belonging to 77 dietary taxa found across the 73 Telfair's skink fecal samples. Introduced taxa were cumulatively consumed more frequently than other categories, accounting for 49.4% of all detections, compared to cryptogenic (20.6%), native (20.6%), and endemic taxa (9.5%). The most frequently consumed introduced species was the ant, Pheidole megacephala, present in 40% of samples. Blue latan palm, Latania loddigesii, was the most frequently consumed endemic species, present in 33% of samples but was only detected in the dry season, when fruits are produced. We found a strong seasonal difference in diet composition explained by the presence of certain plant species solely or primarily in one season and a marked increase in the consumption of animal prey in the dry season. Male and female skinks consumed several taxa at different frequencies. These results present a valuable perspective on the role of introduced species in the trophic network of their invaded ecosystem. Both native and introduced species provide nutritional resources for skinks, and this may have management implications in the context of species conservation and island restoration.
Ecological implications of variable energy storage in the keystone predator, Pisaster ochraceus
Authors: Robles Carlos D. , Molina Mayra , Martinez Carlos Alan , Alvarez Luis
Published: December 2021

We considered how environmental variation and adaption together constrain energy acquisition of a keystone predator and how the constraints might influence its ecological function. We tested the proposition that changing energy availability, occurring as shifts in shore level and size composition of the lower vertical boundary of intertidal mussel beds (Mytilus spp.), affects energy storage and growth of predatory sea stars, Pisaster ochraceus. Energy storage of Pisaster (mass of the pyloric caeca, PC) increased when highly variable inter‐annual mussel recruitment temporarily shifted the lower boundary of the mussel bed down‐shore; energy storage decreased when the lower boundary receded up‐shore. Greatest storage occurred during massive recruitment of juvenile mussels, which caused the largest downward extensions of the boundary. To test the causal basis of the storage–boundary correlation, sea stars collected from sites with natural episodes of massive mussel recruitment were tagged and translocated to sites with experimentally shifted boundaries. On mussel beds with lower boundaries artificially expanded downward, the sea stars sustained high energy storage over most of the range of initial sizes. On mussel beds left unaltered or experimentally recessed, they lost PC mass. The amounts of loss were similar between unaltered and recessed treatments. We suggest an explanation for this unexpected similarity. Pisaster aggregate and disperse in response to the inter‐annual variation in mussel recruitment, and this numerical response is integral to mechanisms holding stationary the lower boundary, imposing stability on the local mussel population. Inter‐annual episodes of massive mussel recruitment, which have the potential to abruptly destabilize the lower boundaries, (1) elicit the strongest numerical response and (2) incur the greatest energy storage. The amount of energy storage in the season of active foraging is approximately proportional to the reproductive output in the subsequent reproductive season. Therefore, we propose that the system property of prey population stability originates in energy constraints underpinning Darwinian fitness of a keystone predator. Study limitations and further tests of the hypothesis are described.
Poly I:C and STING agonist‐primed DC increase lymphoid tissue polyfunctional HIV‐1‐specific CD8+ T cells and limit CD4+ T‐cell loss in BLT mice
Authors: Calvet‐Mirabent Marta , Claiborne Daniel T. , Deruaz Maud , Tanno Serah , Serra Carla , Delgado‐Arévalo Cristina , Sánchez‐Cerrillo Ildefonso , de los Santos Ignacio , Sanz Jesús , García‐Fraile Lucio , Sánchez‐Madrid Francisco , Alfranca Arantzazu , Muñoz‐Fernández María Ángeles , Allen Todd M. , Buzón Maria J. , Balazs Alejandro , Vrbanac Vladimir , Martín‐Gayo Enrique
Published: December 2021

Effective function of CD8+ T cells and enhanced innate activation of DCs in response to HIV‐1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK‐binding Kinase 1 (TBK1) might be useful to acquire controller‐like properties. Here, we evaluated the impact of the combination of 2´3´‐c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV‐1 specific CD8+ T‐cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK‐1 phosphorylation and IL‐12 and IFN‐β expression on DC and increased their ability to activate polyfunctional HIV‐1‐specific CD8+ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ‐DC exhibited less severe CD4+ T‐cell depletion following HIV‐1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to LN, and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV‐1 vaccine studies.
Production and characterization of beer supplemented with Hibiscus sabdariffa (Malvaceae)
Authors: Essiedu Justice A. , Adadi Parise , Kovaleva Elena G.
Published: December 2021

This study evaluated the effect of Hibiscus sabdariffa (HS) (Malvaceae) calyces on fermentation kenetics, phytochemical constituents, volatile organic compounds (VOCs) and sensory profile of beer. Single infusion method of mashing was utilized, and the resulting beers were compared to industrial beers. HS supplementation did not alter the fermentation kenetics as a general decrease in extracts (oBrix) was observed in treated and the control fermentations. The HS beer (HSB) showed higher polyphenols and antioxidant activities than the control Belgian ale beer (BAB) including the industrial beers. One of the industrial beers, BRB showed slightly higher total flavonoid than HSB but not statistically different (p > .05). The peak response of ethyl acetate in HSB (199.61 ± 2.51 × 105 TIC) was significantly (p < .05) higher compared to BAB (22.86 ± 2.01 × 105 TIC). Generally, sensory panelists preferred HSB and BAB over the industrial beers. Therefore, we have demonstrated that supplementing wort with HS during brewing will not alter fermentation performance but augment beer with health promoting phytochemicals.
Immunological alterations after immunotherapy with short lived HBV‐TCR T cells associates with long‐term treatment response in HBV‐HCC
Authors: Tan Anthony Tanoto , Meng Fanping , Jin Jiehua , Zhang Ji‐Yuan , Wang Si‐Yu , Shi Lei , Shi Ming , Li Yuanyuan , Xie Yunbo , Liu Li‐Min , Zhou Chun‐Bao , Chua Alicia , Ho Zi Zong , Luan Junqing , Zhao Jinfang , Li Jing , Wai Lu‐En , Koh Sarene , Wang Tingting , Bertoletti Antonio , Wang Fu‐sheng
Published: December 2021

The application of hepatitis B virus (HBV)–T‐cell receptor (TCR) T‐cell immunotherapy in patients with HBV‐related hepatocellular carcinoma (HBV‐HCC) has been apathetic, as the expression of HBV antigens by both normal HBV‐infected hepatocytes and HCC cells with HBV‐DNA integration increases the risk of on‐target off‐tumor severe liver inflammatory events. To increase the safety of this immunotherapeutic approach, we developed messenger RNA (mRNA) HBV‐TCR‐redirected T cells that—due to the transient nature of mRNA—are functionally short lived and can be infused in escalating doses. The safety of this approach and its clinical potential against primary HBV‐HCC have never been analyzed in human trials; thus, we studied the clinical and immunological parameters of 8 patients with chronic HBV infection and diffuse nonoperable HBV‐HCC treated at weekly intervals with escalating doses (1 × 104, 1 × 105, 1 × 106, and 5 × 106 TCR+ T cells/kg body weight) of T cells modified with HBV‐TCR encoding mRNA. The treatment was well tolerated with no severe systemic inflammatory events, cytokine storm, or neurotoxicity observed in any of these patients throughout treatment. Instead, we observed a destruction of the tumor lesion or a prolonged stable disease in 3 of 8 patients. Importantly, the patients without clinically relevant reductions of HCC did not display any detectable peripheral blood immunological alterations. In contrast, signs of transient localized liver inflammation, activation of the T‐cell compartment, and/or elevations of serum chemokine (C‐X‐C motif) ligand (CXCL) 9 and CXCL10 levels were detected in patients with long‐term clinical benefit. Conclusion: We show that despite the reduced in vivo half‐life (3‐4 days), adoptive transfer of mRNA HBV‐TCR T cells into patients with HBV‐HCC show long‐term clinical benefit that was associated with transient immunological alterations.
Comparative analysis of throughfall observations in six different forest stands: Influence of seasons, rainfall‐ and stand characteristics
Authors: Blume Theresa , Schneider Lisa , Güntner Andreas
Published: December 2021

Throughfall, that is, the fraction of rainfall that passes through the forest canopy, is strongly influenced by rainfall and forest stand characteristics which are in turn both subject to seasonal dynamics. Disentangling the complex interplay of these controls is challenging, and only possible with long‐term monitoring and a large number of throughfall events measured in parallel at different forest stands. We therefore based our analysis on 346 rainfall events across six different forest stands at the long‐term terrestrial environmental observatory TERENO Northeast Germany. These forest stands included pure stands of beech, pine and young pine, and mixed stands of oak‐beech, pine‐beech and pine‐oak‐beech. Throughfall was overall relatively low, with 54–68% of incident rainfall in summer. Based on the large number of events it was possible to not only investigate mean or cumulative throughfall but also its statistical distribution. The distributions of throughfall fractions show distinct differences between the three types of forest stands (deciduous, mixed and pine). The distributions of the deciduous stands have a pronounced peak at low throughfall fractions and a secondary peak at high fractions in summer, as well as a pronounced peak at higher throughfall fractions in winter. Interestingly, the mixed stands behave like deciduous stands in summer and like pine stands in winter: their summer distributions are similar to the deciduous stands but the winter peak at high throughfall fractions is much less pronounced. The seasonal comparison further revealed that the wooden components and the leaves behaved differently in their throughfall response to incident rainfall, especially at higher rainfall intensities. These results are of interest for estimating forest water budgets and in the context of hydrological and land surface modelling where poor simulation of throughfall would adversely impact estimates of evaporative recycling and water availability for vegetation and runoff.
A multi‐scale study of the dominant catchment characteristics impacting low‐flow metrics
Authors: Floriancic Marius G. , Spies Daniel , van Meerveld Ilja H. J. , Molnar Peter
Published: December 2021

Low flows can impact water use and instream ecology. Therefore, reliable predictions of low‐flow metrics are crucial. In this study, we assess which catchment characteristics (climate, topography, geology and landcover) can explain the spatial variability of low‐flow metrics at two different scales: the regional scale and the small headwater catchment scale. For the regional‐scale analysis, we calculated the mean 7‐day annual minimum flow (qmin), the mean of the flow that is exceeded 95% of the year (q95), and the master recession constant (C) for 280 independent gauging stations across the Swiss Plateau and the Swiss Alps for the 2000–2018 period. We assessed the relation between 44 catchment characteristics and the three low‐flow metrics based on correlation analysis and a random forest model. Low‐flow magnitudes across the Swiss Plateau were positively correlated with the fraction of the area covered by sandstone bedrock or alluvium, and with the area that has a slope between 10° and 30°. Across the Swiss Alps, low‐flow magnitudes were positively correlated with the fraction of area with slopes between 30° and 60°, and the area with glacial deposits and debris cover. There was good agreement between observations and predictions by the random forest regression model with the top 11 catchment characteristics for both regions: for 80% of the Swiss Plateau catchments and 60% of the Swiss Alpine catchments, we could predict the three low‐flow metrics within an error of 30%. The residuals of the regression model, however, varied across short distances, suggesting that local catchment characteristics affect the variability of low‐flow metrics. For the local‐scale headwater catchments, we conducted 1‐day snapshot field campaigns in 16 catchments during low‐flow periods in 2015 and 2016. The measurements in these sub‐catchments also showed that areas with sandstone bedrock and a good storage‐to‐river connectivity had above average low‐flow magnitudes. Including knowledge on local catchment characteristics may help to improve regional low‐flow predictions, however, not all local catchment characteristics were useful descriptors at larger scales.
Cancer risk in patients with bipolar disorder and unaffected siblings of such patients: A nationwide population‐based study
Authors: Chen Mu‐Hong , Tsai Shih‐Jen , Su Tung‐Ping , Li Cheng‐Ta , Lin Wei‐Chen , Cheng Chih‐Ming , Chen Tzeng‐Ji , Bai Ya‐Mei
Published: December 2021

Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age‐matched unaffected siblings of patients with bipolar disorder and 101 422 age‐matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio [OR] = 1.22, 95% confidence interval [CI]: [1.06, 1.40]) and unaffected siblings of such patients (OR = 1.17, 95% CI [1.02, 1.34]) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI [1.38, 2.61]) and unaffected siblings (OR = 1.65, 95% CI [1.19, 2.28]), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients.
Fathers’ experiences of fetal attachment: A qualitative study
Authors: Lagarto Ana , Duaso Maria J.
Published: December 2021

Paternal‐fetal attachment (PFA) is associated with the degree of emotional support offered by fathers during pregnancy and has implications for the safety and quality of a mother's labor and postnatal experiences. This study explored fathers’ experiences of PFA including their understanding of the phenomenon and its manifestation. Data were collected through interviews with 10 fathers‐to‐be and analysis followed an interpretative phenomenological approach. Four themes emerged from the data: trigger moment; awareness of responsibility; transition to fatherhood; and emotional conflict. Most fathers experienced a trigger moment that made the reality of having a baby clear to them and which initiated or intensified feelings of attachment toward the fetus. Male family relatives, friends with children, and antenatal education groups provided support to expectant fathers. However, they felt quite lost in their role and some believed there was insufficient support for their mental health. Findings suggest that different situations can trigger the attachment process and that fathers longed to be included in perinatal care but experienced a lack of support. Raising awareness of the importance of PFA can help initiate the process in fathers and better equip them to contribute during the antenatal period and to future child development.
Automated detection of apoptotic versus nonapoptotic cell death using label‐free computational microscopy
Authors: Kabir Md Alamgir , Kharel Ashish , Malla Saloni , Kreis Zachary Joseph , Nath Peuli , Wolfe Jared Neil , Hassan Marwa , Kaur Devinder , Sari‐Sarraf Hamed , Tiwari Amit K. , Ray Aniruddha
Published: December 2021

Identification of cell death mechanisms, particularly distinguishing between apoptotic versus nonapoptotic pathways, is of paramount importance for a wide range of applications related to cell signaling, interaction with pathogens, therapeutic processes, drug discovery, drug resistance, and even pathogenesis of diseases like cancers and neurogenerative disease among others. Here, we present a novel high‐throughput method of identifying apoptotic versus necrotic versus other nonapoptotic cell death processes, based on lensless digital holography. This method relies on identification of the temporal changes in the morphological features of mammalian cells, which are unique to each cell death processes. Different cell death processes were induced by known cytotoxic agents. A deep learning‐based approach was used to automatically classify the cell death mechanism (apoptotic vs necrotic vs nonapoptotic) with more than 93% accuracy. This label free approach can provide a low cost (<$250) alternative to some of the currently available high content imaging‐based screening tools.
Framework of anti‐racist school counseling competencies: A Delphi study
Authors: Stickl Haugen Jaimie , Bledsoe Kenya G. , Burgess Melanie , Rutledge Marsha L.
Published: December 2021

The current sociopolitical climate of the United States has heightened awareness around the need for school counselors to engage in anti‐racist practices in order to address racism within schools; however, there is a lack of guidance around anti‐racist counseling competency. The purpose of this Delphi research study was to develop an initial list of empirically based anti‐racist school counseling competencies to support school counseling professionals. An expert panel of school counselors, directors, and counselor educators reached a consensus on 180 items across 5 categories including specific aspects of awareness, attitudes, knowledge, characteristics, and behaviors needed to dismantle racism and promote equity in schools. Considerations for school counselors, supervisors, and counselor educators are discussed.
Using projection operators with maximum overlap methods to simplify challenging self‐consistent field optimization
Authors: Corzo Hector H. , Abou Taka Ali , Pribram‐Jones Aurora , Hratchian Hrant P.
Published: December 2021

Maximum overlap methods are effective tools for optimizing challenging ground‐ and excited‐state wave functions using self‐consistent field models such as Hartree‐Fock and Kohn‐Sham density functional theory. Nevertheless, such models have shown significant sensitivity to the user‐defined initial guess of the target wave function. In this work, a projection operator framework is defined and used to provide a metric for non‐aufbau orbital selection in maximum‐overlap‐methods. The resulting algorithms, termed the Projection‐based Maximum Overlap Method (PMOM) and Projection‐based Initial Maximum Overlap Method (PIMOM), are shown to perform exceptionally well when using simple user‐defined target solutions based on occupied/virtual molecular orbital permutations. This work also presents a new metric that provides a simple and conceptually convenient measure of agreement between the desired target and the current or final SCF results during a calculation employing a maximum‐overlap method.
A comparison of transdiagnostic behavior therapy (TBT) and behavioral activation treatment for depression (BATD) in veterans with major depressive disorder
Authors: Gros Daniel F. , Coyne Alice E.
Published: December 2021

Objectives

Although frequently discussed within the scope of transdiagnostic psychotherapy protocols, limited data are available on their efficacy in patients with a principal diagnosis of major depressive disorder. The present study attempted to address that gap in the literature through a randomized clinical trial comparing transdiagnostic behavior therapy (TBT) to behavioral activation treatment for depression (BATD).

Methods

Forty veterans with principal major depressive disorder were randomized into either 12 sessions of individual TBT or BATD, with symptom measures collected at baseline and posttreatment. Process variables for treatment engagement and completion also were recorded.

Results

Participants reported similar symptom improvements in depression, stress, anhedonia, and impairment across both treatments. Clinician‐rated treatment improvements favored TBT. Participants in TBT also attended more appointments, canceled or missed fewer appointments, and completed the protocol at a higher rate than participants that received BATD.

Conclusions

The present findings support TBT as an efficacious treatment for principal major depressive disorder, with potentially superior coverage of comorbid anxiety symptomatology and improved treatment adherence and completion compared to BATD. Pending replication in larger samples, TBT and other similar transdiagnostic psychotherapies should be considered for implementation across the anxiety and depressive disorders to simplify dissemination efforts for evidence‐based psychotherapies and potentially improve coverage of comorbidity.
Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy
Authors: Duran‐Trio Lara , Fernandes‐Pires Gabriella , Grosse Jocelyn , Soro‐Arnaiz Ines , Roux‐Petronelli Clothilde , Binz Pierre‐Alain , De Bock Katrien , Cudalbu Cristina , Sandi Carmen , Braissant Olivier
Published: December 2021

Creatine (Cr) is a nitrogenous organic acid and plays roles such as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes arginine:glycine amidinotransferase and guanidinoacetate methyltransferase, and specifically taken up by the transporter SLC6A8. Loss‐of‐function mutations in the genes encoding for the enzymes or the transporter cause creatine deficiency syndromes (CDS). CDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. Among CDS, the X‐linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies, and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models, and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8Y389C knock‐in rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency, and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co‐occurred with both nervous and muscle dysfunctions, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.
OMICRON (B.1.1.529): A new SARS‐CoV‐2 variant of concern mounting worldwide fear
Authors: Thakur Vikram , Ratho Radha Kanta
Published: December 2021

Recent emergence of the SARS‐CoV‐2 variant as OMICRON has become a global concern. This short note highlights the identification and global spread of OMICRON which has spread over 77 nations by now, which resulted in many hypotheses about its origin and degree of infectivity. The detection of mutations in the RBD region of Spike protein is a concern by surpassing vaccine immunity. The ahead will speak about its transmission potentiality, infectivity, disease morbidity as well as its effect on COVID‐19 vaccines.
Homeostatic regulation of neuronal excitability by probiotics in male germ‐free mice
Authors: Kim Juhyun , Kim Dong Won , Lee Adrian , Mason Madisen , Jouroukhin Yan , Woo Hyewon , Yolken Robert H. , Pletnikov Mikhail V.
Published: December 2021

Emerging evidence indicates that probiotics can influence the gut–brain axis to ameliorate somatic and behavioral symptoms associated with brain disorders. However, whether probiotics have effects on the electrophysiological activities of individual neurons in the brain has not been evaluated at a single‐neuron resolution, and whether the neuronal effects of probiotics depend on the gut microbiome status have yet to be tested. Thus, we conducted whole‐cell patch‐clamp recording‐assisted electrophysiological characterizations of the neuronal effects of probiotics in male germ‐free (GF) mice with and without gut microbiome colonization. Two weeks of treatment with probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis) significantly and selectively increased the intrinsic excitability of hippocampal CA1 pyramidal neurons, whereas reconstituting gut microbiota in GF mice reversed the effects of the probiotics leading to a decreased intrinsic excitability in hippocampal neurons. This bidirectional modulation of neuronal excitability by probiotics was observed in hippocampal neurons with corresponding basal membrane property and action potential waveform changes. However, unlike the hippocampus, the amygdala excitatory neurons did not show any electrophysiological changes to the probiotic treatment in either GF or conventionalized GF mice. Our findings demonstrate for the first time how probiotic treatment can have a significant influence on the electrophysiological properties of neurons, bidirectionally modulating their intrinsic excitability in a gut microbiota and brain area‐specific manner.
Stack design of OLEDs with high performance and simplified device structures
Authors: Wang Jing , Pang Huiqing , Cui Zhihao , Chen Xiao , Zheng Renjie , Kwong Raymond , Xia Sean
Published: December 2021

The increasingly complex layer structure of commercial Organic Light Emitting Devices (OLEDs) leads to higher manufacturing costs. In this paper, we demonstrate a simplified device structure with only two layers between the anode and the emissive layer, compared with the usual three or four layers in state‐of‐the‐art devices. The stack is designed so as to ensure efficient hole injection and transport. As a result, the devices achieve longer lifetime and higher efficiency, than the more complex structure, while maintaining equivalent chromaticity and a comparable operating voltage. Such a performance trend is observed in all three RGB colors, in both bottom and top emission devices, as well as in tandem devices. Fewer layers help cost‐effective mass production, and we demonstrate that such simplified device structure has a great potential in both OLED display and lighting applications.
Characterization of a highly stable zwitterionic hydrophilic interaction chromatography stationary phase based on hybrid organic–inorganic particles
Authors: Walter Thomas H. , Alden Bonnie A. , Berthelette Kenneth , Field Jessica A. , Lawrence Nicole L. , McLaughlin Justin , Patel Amit V.
Published: December 2021

We have characterized a sulfobetaine stationary phase based on 1.7 μm ethylene‐bridged hybrid organic–inorganic particles, which is intended for use in hydrophilic interaction chromatography. The efficiency of a column packed with this material was determined as a function of flow rate, demonstrating a minimum reduced plate height of 2.4. The batch‐to‐batch reproducibility was assessed using the separation of a mixture of acids, bases, and neutrals. We compared the retention and selectivity of the hybrid sulfobetaine stationary phase to that of several benchmark materials. The hybrid sulfobetaine material gave strong retention for polar neutrals and high selectivity for methyl groups, hydroxy groups, and configurational isomers. Large differences in cation and anion retention were observed among the columns. We characterized the acid and base stability of the hybrid sulfobetaine stationary phase, using accelerated tests at pH 1.3 and 11.0, both at 70°C. The results support a recommended pH range of 2–10. We also investigated the performance of columns packed with this material for metal‐sensitive analytes, comparing conventional stainless steel column hardware to hardware that incorporates hybrid surface technology to mitigate interactions with metal surfaces. Compared to the conventional columns, the hybrid surface technology columns showed a greatly improved peak shape.
10 Gbit s−1 Free Space Data Transmission at 9 µm Wavelength With Unipolar Quantum Optoelectronics
Authors: Dely Hamza , Bonazzi Thomas , Spitz Olivier , Rodriguez Etienne , Gacemi Djamal , Todorov Yanko , Pantzas Konstantinos , Beaudoin Grégoire , Sagnes Isabelle , Li Lianhe , Davies Alexander Giles , Linfield Edmund H. , Grillot Frédéric , Vasanelli Angela , Sirtori Carlo
Published: December 2021

Free space optics data transmission with bitrate in excess of 10 Gbit s−1 is demonstrated at 9 µm wavelength by using a unipolar quantum optoelectronic system at room temperature, composed of a quantum cascade laser, a modulator, and a quantum cascade detector. The large frequency bandwidth of the system is set by the detector and the modulator that are both high frequency devices, while the laser emits in continuous wave. The amplitude modulator relies on the Stark shift of an absorbing optical transition in and out of the laser frequency. This device is designed to avoid charge displacement, and therefore it is characterized by an intrinsically large bandwidth and very low electrical power consumption. This demonstration of high‐bitrate data transmission sets unipolar quantum devices as the most performing platform for the development of optoelectronic systems operating at very high frequency in the mid‐infrared for several applications, such as digital communications and high‐resolution spectroscopy.
Single‐Shot Reference‐Free Holographic Imaging using a Liquid Crystal Geometric Phase Diffuser
Authors: Oh Jeonghun , Lee KyeoReh , Park YongKeun
Published: December 2021

It has been recently demonstrated that wavefront information can be directly measured using the speckle‐correlation scattering method. The realization of speckle‐correlation scattering requires the use of a diffusive layer; however, it poses technical challenges in characterizing the transmission matrix of the diffusive layer or precisely fabricating an engineered random metasurface. Herein, liquid crystal geometric phase diffusers are exploited for single‐shot reference‐free holographic imaging based on speckle‐correlation scattering. It is demonstrated that the use of a commercial geometric phase diffuser provides precise holographic measurements in a simple imaging setup, with no calibration required. This low‐cost, simple, and high‐resolution wavefront sensing approach inspired by liquid crystal materials may find direct applications in metrology, industrial inspection, and biophotonics.
Heterogeneous Bubble Nucleation by Homogeneous Crystal Nuclei in Poly(l‐Lactic Acid) Foaming
Authors: Longo Alessandra , Di Maio Ernesto , Di Lorenzo Maria Laura
Published: December 2021

A novel method to enhance and control bubble nucleation in poly(l‐lactic acid) (PLLA) foaming, not relying on external nucleating agents, is presented. Amorphous PLLA is annealed at temperatures close to its glass transition, to allow local alignment of polymer chains in the form of nanosized aggregates, called homogeneous crystal nuclei (HCN). PLLA containing HCN is then foamed after sorption of CO2 at 120 °C and 10 MPa. Under the chosen experimental conditions, HCN can promote growth of PLLA spherulites that can be controlled by thermal‐pressure history. Foam morphology is strongly affected by the presence of HCN, which act as heterogeneous nucleation sites for bubbles. Resulting foams are characterized by a bimodal morphology, with bubbles of about 50–70 µm in diameter developed in the bulk, and much smaller cells of few µm, grown upon pre‐existing crystal aggregates. The method detailed here to attain PLLA foams with tailored morphology can be exploited also for other semicrystalline polymers.
LIVECHART Patient‐Reported Outcome Tool for Botulinum Toxin Treatment in Cervical Dystonia
Authors: Chueluecha Chuenchom , Moore Austen Peter
Published: December 2021

Background

Many tools used for recording the response to botulinum toxin treatment are disease‐specific, observer‐based and cumbersome to implement in service settings, especially where clinics treat a variety of disorders. Physicians, clinics, researchers, and patients themselves could benefit from a practical and generic patient‐reported outcome tool. The Liverpool botulinum toxin effects chart (LIVECHART) is a patient‐administered questionnaire developed and used informally over 25 years in a major UK botulinum toxin treatment clinic. In preparation for more formal validation studies, this cross‐sectional study aimed to understand how well LIVECHART captures the effects of botulinum toxin treatment, using patients with cervical dystonia as exemplars.

Methods

LIVECHART questionnaires were completed by 90 patients with cervical dystonia who had each experienced at least three previous botulinum toxin injection cycles with completed LIVECHARTs.

Results

There were significant positive correlations between Likert scores (major deterioration—major benefit) for botulinum toxin treatment effects, and measures derived from weekly visual analog scale (VAS) scores (0–100), including (1) baseline to peak effect, (2) Area Under the benefit Curve (AUC) of current cycle, (3) peak effect duration, (4) duration of acceptable benefit, (5) time back to baseline. The AUC of the current cycle was positively correlated with (1) VAS change baseline to peak effect, and (2) week worn off completely.

Conclusions

We conclude that LIVECHART has high internal consistency and reliability. It adequately reflects amplitude, duration and overall benefit of botulinum toxin treatment, and is worth further formal evaluation to determine its validity and reliability.
Supply chain contracting with competing regretful retailers
Authors: Kirshner Samuel N. , Li Zhaolin
Published: December 2021

We study a two‐tier supply chain with demand uncertainty where retailers experience regret from ex‐post inventory error. With a monopolist retailer, we find that individual rationality can lead to supply chain coordination and creates non‐trivial differences between regret and other reference points previously shown to be mathematically equivalent. Under competition, inventory regret can lead to either a separating or a pooling equilibrium despite the heterogeneity in their disutility from regret. The potential for a separating or pooling equilibria also differs substantially from the extant literature with implications for the wholesale price contracts and how competition dynamics impact industry service levels.
Applications of statistically probability convergence to approximation theorem
Authors: Jasrotia Swati , Singh Uday Pratap , Raj Kuldip
Published: December 2021

The purpose of this article is to study and investigate statistically probability convergence for the sequence of random variables by virtue of deferred Nörlund and deferred Euler summability mean. With the aid of MATLAB software, we also graphically exhibit the probability convergence for probability density function of random variables. Further, as an application of our newly formed summability mean, we prove Korovkin‐type approximation theorem via deferred Nörlund and deferred Euler statistically probability convergence and present compelling instances to illustrate the findings.
The use of DOSY experiments to determine the solution structures of coinage metal pyrazolates: The case of {[3,5‐(CF3)2Pz]Ag}3
Authors: Alkorta Ibon , Benito María Teresa , Elguero José , Doyagüez Elisa García , Patterson Monika R. , Jimeno María Luisa , Dias H. V. Rasika , Reviriego Felipe
Published: December 2021

A series of DOSY experiments have been carried out to determine the solution stoichiometry of silver(I) 3,5‐bis (trifluoromethyl)pyrazolate species. This compound exists as a trimer in the solid state (n = 3) but in solutions of chlorinated solvents, the DOSY data suggest the presence of a mixture of solvent stabilized monomer (n = 1) and dimer (n = 2) in equilibrium. Different approximations have been used including the Stokes–Einstein and the Stokes–Einstein–Gierer–Wirtz equations. Some methodological problems are discussed.
Multimorbidity and healthcare utilization among Black Americans: A cross‐sectional study
Authors: Ahn Sangwoo , Bartmess Marissa , Lindley Lisa C.
Published: December 2021

Aim

Racial disparities between multimorbidity presence and healthcare utilization are present within the United States, but less is known about the relationship between multimorbidity presence and healthcare utilization among Black Americans. This study was conducted to examine the relationship between multimorbidity and healthcare utilization among Black Americans.

Design

Cross‐sectional study.

Methods

This study (n = 425, 57% female) used adult level data from the 2012–2013 Connecticut Health Care Survey.

Results

Multivariate logistic regressions indicated that multimorbidity presence predicted a doctor and a specialist visit, but not a dentist visit.

Conclusion

This study identified multimorbidity presence as a predictor for healthcare utilization, but further research is necessary to understand healthcare utilization experiences among Black Americans with multimorbidity to assess the quality of care. Appropriate measures should also be considered to increase access to dental care for Black Americans with multimorbidity.