bluuebunny/crossref_metadata_2025 huggingface dataset:
Boronic Acid‐Mediated Photocatalysis Enables the Intramolecular Hydroacylation of Olefins Using Carboxylic Acids
Authors: Yumura Taichi , Nanjo Takeshi , Takemoto Yoshiji
Published: March 2022

An intramolecular hydroacylation of olefins using carboxylic acids (CAs) has been developed. With the aid of a boronic acid, CAs can be used as acyl‐radical precursors in catalytic photoredox reactions driven by visible light. The CAs are easily converted into their corresponding cyclic ketones without the need to use any stoichiometric activating reagents. Mechanistic studies implied that the formation of an “ate” complex from the CA and boronic acid is crucial for the generation of the acyl radical equivalent from the unreactive carboxy group.
Synthesis of Carbon‐ and Nitrogen‐Substituted 5‐ and 6‐Membered Benzophostams
Authors: Sabourin Axel , Dufour Jeremy , Vors Jean‐Pierre , Bernier David , Montchamp Jean‐Luc
Published: March 2022

Previously, the synthesis of the novel 6‐membered and a series of P‐substituted 5‐membered benzophostams was accomplished. Here, the synthesis of N‐ and C‐substituted benzophostams is presented. For N‐substitution, alkylation was accomplished using the heterocycle, LiHMDS and an alkyl halide, or alternatively by copper‐catalyzed cyclization of the N‐alkyl phosphonamide. N‐Arylation could similarly be accomplished on the preformed heterocycle or on the phosphonamide precursor via copper‐catalyzed cross‐coupling. Dimethylation at the benzylic position could be conducted with LiHMDS and methyl iodide. However, due to the significant cost of LiHMDS, a much less expensive and more efficient alternative approach was developed relying on a palladium‐catalyzed reductive Heck reaction.
A Triboelectric Piston–Cylinder Assembly with Condition‐Monitoring and Self‐Powering Capabilities
Authors: Li Guoxing , Wu Hongyu , Guo Rui , Zhang Hulin , Li Lintao , Iqbal Muhammad Yousaf , Gu Fengshou
Published: March 2022

The condition monitoring of piston–cylinder‐reciprocating machinery usually relies on vibration and acoustic sensors installed on the outer surface of cylinders. However, vibration and acoustic signals are susceptible to external interference from other accessories, and require an external power supply, which limits its widespread application. Herein, based on the lateral sliding mode of triboelectric nanogenerator (TENG), a novel reciprocating device with condition‐monitoring and self‐powering capabilities is proposed, called piston–cylinder triboelectric nanogenerator (PCTN). The effects of different factors, including mean piston speed, number of piston rings, materials of piston ring and cylinder, on the output characteristics of PCTN are investigated, respectively. Two typical fault cases, that is, piston ring missing and coil fracture, are investigated to verify the condition‐monitoring capability of PCTN. Piston ring missing faults can be effectively identified based on the variations in peak and root‐mean‐square (RMS) values of short‐circuit current (I
sc). Coil fracture faults can be identified and located by analyzing changes in time–domain curve and time–‐frequency spectrum of I
sc. Herein, a theoretical and experimental basis for the widespread application of PCTN in reciprocating machinery is provided.
Cognitive and quality‐of‐life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment‐refractory chronic anorexia nervosa
Authors: Pérez Víctor , Villalba‐Martínez Gloria , Elices Matilde , Manero Rosa María , Salgado Purificación , Ginés José María , Guardiola Rocío , Cedrón Carlos , Polo María , Delgado‐Martínez Ignacio , Conesa Gerardo , Medrano Santiago , Portella Maria J.
Published: March 2022

Background

Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment‐resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN.

Methods

Eight patients with severe, chronic, treatment‐resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6‐month after surgery.

Findings

Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning.

Interpretation

These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.
Nobiletin enhances plasma Interleukin‐6 and C‐X‐C motif chemokine ligand 1 levels that are increased by treadmill running
Authors: Suzuki Toshihide , Shimizu Makoto , Yamauchi Yoshio , Sato Ryuichiro
Published: March 2022

Exercise increases the muscular secretion of Interleukin‐6 (IL‐6), which is partially regulated by β2‐adrenergic receptor signaling. Nobiletin is a polymethoxyflavone (PMF) found in citrus fruits that induces the secretion of IL‐6 from C2C12 myotubes, but it remains unclear whether nobiletin promotes IL‐6 secretion during exercise. The aim of this study was to clarify the effects of nobiletin on IL‐6 secretion during exercise. Nobiletin and epinephrine were found to synergistically increase IL‐6 secretion from differentiated C2C12 cells, which was suppressed by the inhibition of adenylyl cyclase (AC) or protein kinase A (PKA). Treadmill running for 60 min increased plasma levels of IL‐6, epinephrine, and norepinephrine in rats. Nobiletin (5 mg/kg) orally administered 30 min before running increased plasma IL‐6 levels further, although it did not increase plasma epinephrine and norepinephrine. In a similar manner to IL‐6, nobiletin and epinephrine synergistically increased the secretion of C‐X‐C motif chemokine ligand 1 (CXCL‐1) from C2C12 cells, or the increase in plasma CXCL‐1 was enhanced by nobiletin after treadmill running of rats. Our results suggest that nobiletin promotes IL‐6 and CXCL‐1 secretion from skeletal muscle by synergistic enhancement of the PKA pathway in β2‐adrenergic receptor signaling.
Endocannabinoid signaling in glioma
Authors: Costas‐Insua Carlos , Guzmán Manuel
Published: March 2022

High‐grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti‐tumoral effects by modulating key intracellular signaling pathways. The mechanism of this cannabinoid receptor‐evoked anti‐tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell‐like properties of cancer cells, thereby affecting the complex tumor microenvironment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context‐dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid‐based anti‐tumoral therapies, as well as the preliminary clinical testing that is currently underway.
A comparison of two approaches for modeling dementia progression in a changing patient context
Authors: Wubben Nina , Haaksma Miriam , Ramakers Inez H. G. B. , van der Flier Wiesje M. , Verhey Frans R. J. , Olde Rikkert Marcel G. M. , Melis René J. F.
Published: March 2022

Objectives

To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time‐varying comorbidity and frailty.

Methods

We used individual growth models to study baseline and time‐varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini‐Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS‐G).

Results

Although baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time‐varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9‐point lower MMSE score (p = 0.03) and a 14.9‐point lower DAD score (p < 0.01). A 1‐point increase in CIRS‐G score was associated with a 1.1‐point lower DAD score (p < 0.01).

Conclusions

Time‐varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context.
Impact of COVID‐19 on carers of people with dementia in the community: Findings from the British IDEAL cohort
Authors: Quinn Catherine , Gamble Laura D. , Parker Sophie , Martyr Anthony , Collins Rachel , Victor Christina , Dawson Eleanor , Hunt Anna , Pentecost Claire , Allan Louise , Clare Linda
Published: March 2022

Objective

Unpaid carers for people with dementia play a crucial role in society. Emerging evidence suggests the COVID‐19 pandemic has negatively impacted on carers. This study sought to explore the impact of the COVID‐19 pandemic on carers for community‐dwelling people with dementia and compare responses with pre‐pandemic data.

Methods

Data were collected between September 2020 and April 2021 in England and Wales. Carers were identified from the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort and data were collected either through the telephone, video conferencing, or an online questionnaire. Responses from 242 carers were compared against benchmark data from the IDEAL cohort collected pre‐pandemic. Analyses were conducted for the full sample of carers and spousal/partner carers only.

Results

In total 48.8% of carers thought their healthcare needs were negatively affected during the pandemic. Compared with pre‐pandemic data carers were more lonely and experienced less life satisfaction. There was little impact on carers' experience of caregiving, although carers felt trapped in their caregiving role. Carers were more optimistic and had higher social contact with relatives. There were changes in the methods carers used for contacting relatives and friends. Most carers coped very or fairly well during the pandemic. There was little difference in the experiences of spousal/partner carers and the full sample.

Conclusions

After a long period of providing care under pandemic conditions carers require additional support. This support needs to be focused on alleviating feelings of loneliness and increasing life satisfaction. Services need to consider how to improve access to health care, particularly resuming face‐to‐face appointments.
The effect on dental care utilization from transitioning pediatric Medicaid beneficiaries to managed care
Authors: Nasseh Kamyar , Bowblis John R.
Published: March 2022

Compared to the fee‐for‐service (FFS) model, the managed care delivery system has the potential to improve health care management, increase provider accountability, and support better monitoring of health care quality. However, managed care organizations may attempt to control costs by curbing utilization among Medicaid beneficiaries or reducing reimbursement for Medicaid services. It is an empirical question whether managed care increases or decreases utilization of services. Using detailed pediatric public insurance dental claims data from 2016 through 2018, we examined whether the transition from FFS to managed care affects rates of dental care utilization. Between 2016 and 2018, Indiana, Missouri and Nebraska transitioned pediatric Medicaid beneficiaries from public dental fee‐for‐service programs to private managed care entities. Using an extended two‐way fixed‐effects estimation framework, we found that dental managed care leads to a decline in dental care utilization, especially when compared to states that maintain FFS provision of Medicaid dental services.
“Affirming” journey: Narrative review and practice considerations on gender affirming care
Authors: Mills Alex R. , Astle Kevin , Frazier Cheyenne C.
Published: March 2022

There is a growing interest in the healthcare community to focus on the healthcare needs of lesbian, gay, bisexual, transgender, or genderqueer (LGBTQ) patients, particularly transgender and gender diverse (TGD) patients. TGD individuals have historically experienced rejection and mistreatment by healthcare providers yet have significant health needs, highlighting the need for providing affirming care. Medication therapy for TGD individuals involves many nuances and special considerations for managing concomitant therapies and drug interactions. Additionally, approaches to caring for TGD patients involve both medical interventions as well as social and legal processes. Pharmacists can assist and facilitate the care for TGD patients through a variety of mechanisms. This narrative review describes strategies to recognize and address many aspects of the care for TGD individuals, including destigmatizing care, affirmation strategies, and an overview of therapeutic misconceptions and concerns. Ultimately, this manuscript serves as a guide for pharmacists to care holistically for TGD patients.
Reorganization of prefrontal network in stroke patients with dyskinesias: evidence from resting‐state functional near‐infrared spectroscopy
Authors: Pang Richong , Wang Dan , Chen Tara Scarlette Rosalyn , Yang Anping , Yi Li , Chen Sisi , Wang Jie , Wu Kai , Zhao Chaochao , Liu Hua , Ai Yilong , Yang Aoran , Sun Jinyan
Published: March 2022

Stroke usually causes multiple functional disability. To develop novel rehabilitation strategies, it is quite necessary to improve the understanding of post‐stroke brain plasticity. Here, we use functional near‐infrared spectroscopy to investigate the prefrontal cortex (PFC) network reorganization in stroke patients with dyskinesias. The PFC hemodynamic signals in the resting state from 16 stroke patients and 10 healthy subjects are collected and analyzed with the graph theory. The PFC networks for both groups show small‐world attributes. The stroke patients have larger clustering coefficient and transitivity and smaller global efficiency and small‐worldness than healthy subjects. Based on the selected network features, the established support vector machine model classifies the two groups of subjects with an accuracy rate of 88.5%. Besides, the clustering coefficient and local efficiency negatively correlate with patients' motor function. This study suggests that the PFC of stroke patients with dyskinesias undergoes specific network reorganization.
Comparative evaluation of mesenchymal stromal cell growth and osteogenic differentiation on a shape memory polymer scaffold
Authors: Stukel Shah Jessica M. , Lundquist Bridney , Macaitis Joseph , Pfau‐Cloud Michaela R. , Beltran Felipe O. , Grunlan Melissa A. , Lien Wen , Wang Heuy‐Ching , Burdette Alexander J.
Published: March 2022

Trauma‐induced, critical‐size bone defects pose a clinical challenge to heal. Albeit autografts are the standard‐of‐care, they are limited by their inability to be shaped to various defect geometries and often incur donor site complications. Herein, the combination of a “self‐fitting” shape memory polymer (SMP) scaffold and seeded mesenchymal stromal cells (MSCs) was investigated as an alternative. The porous SMP scaffold, prepared from poly(ε‐caprolactone) diacrylate (PCL‐DA) and coated with polydopamine, provided conformal shaping and cell adhesion. MSCs from five tissues, amniotic (AMSCs), chorionic tissue (CHSCs), umbilical cord (UCSCs), adipose (ADSCs), and bone marrow (BMSCs) were evaluated for viability, density, and osteogenic differentiation on the SMP scaffold. BMSCs exhibited the fastest increase in cell density by day 3, but after day 10, CHSCs, UCSCs, and ADSCs approached similar cell density. BMSCs also showed the greatest calcification among the cell types, followed closely by ADSCs, CHSCs and AMSCs. Alkaline phosphatase (ALP) activity peaked at day 7 for AMSCs, UCSCs, ADSCs and BMSCs, and at day 14 for CHSCs, which had the greatest overall ALP activity. Of all the cell types, only scaffolds cultured with ADSCs in osteogenic media had increased hardness and local modulus as compared to blank scaffolds after 21 days of cell culture and osteogenic differentiation. Overall, ADSCs performed most favorably on the SMP scaffold. The SMP scaffold was able to support key cellular behaviors of MSCs and could potentially be a viable, regenerative alternative to autograft.
Towards improved FAIRness of the ThermoML Archive
Authors: Riccardi Demian , Trautt Zachary , Bazyleva Ala , Paulechka Eugene , Diky Vladimir , Magee Joseph W. , Kazakov Andrei F. , Townsend Scott A. , Muzny Chris D.
Published: March 2022

The ThermoML Archive is a subset of Thermodynamics Research Center (TRC) data holdings corresponding to cooperation between NIST TRC and five journals: Journal of Chemical Engineering and Data (ISSN: 1520‐5134), The Journal of Chemical Thermodynamics (ISSN: 1096‐3626), Fluid Phase Equilibria (ISSN: 0378‐3812), Thermochimica Acta (ISSN: 0040‐6031), and International Journal of Thermophysics (ISSN: 1572‐9567). Data from initial cooperation (around 2003) through the 2019 calendar year are included. The archive has undergone a major update with the goal of improving the FAIRness and user experience of the data provided by the service. The web application provides comprehensive property browsing and searching capabilities; searching relies on a RESTful API provided by the Cordra software for managing digital objects. JSON files with a schema derived from ThermoML are provided as an additional serialization to lower the barrier to programmatic consumption of the information, for stakeholders who may have a preference of JSON over XML. The ThermoML and JSON files for all available entries can be downloaded from data.nist.gov (https://data.nist.gov/od/id/mds2-2422).
Conformations and binding pockets of HRas and its guanine nucleotide exchange factors complexes in the guanosine triphosphate exchange process
Authors: Xiong Yuqing , Zeng Juan , Xia Fei , Cui Qiang , Deng Xianming , Xu Xin
Published: March 2022

The human Son of Sevenless (SOS) activates the signal‐transduction protein Ras by forming the complex SOS·Ras and accelerating the guanosine triphosphate (GTP) exchange in Ras. Inhibition of SOS·Ras could regulate the function of Ras in cells and has emerged as an effective strategy for battling Ras related cancers. A key factor to the success of this approach is to understand the conformational change of Ras during the GTP exchange process. In this study, we perform an extensive molecular dynamics simulation to characterize the specific conformations of Ras without and with guanine nucleotide exchange factors (GEFs) of SOS, especially for the substates of State 1 of HRasGTP∙Mg2+. The potent binding pockets on the surfaces of the RasGDP∙Mg2+, the S1.1 and S1.2 substates in State 1 of RasGTP∙Mg2+ and the ternary complexes with SOS are predicted, including the binding sites of other domains of SOS. These findings help to obtain a more thorough understanding of Ras functions in the GTP cycling process and provide a structural foundation for future drug design.
On a relation between bipartite biregular cages, block designs and generalized polygons
Authors: Araujo‐Pardo Gabriela , Jajcay Robert , Ramos‐Rivera Alejandra , Szőnyi Tamás
Published: March 2022

A bipartite biregular ‐graph is a bipartite graph of even girth having the degree set and satisfying the additional property that the vertices in the same partite set have the same degree. An ‐bipartite biregular cage is a bipartite biregular ‐graph of minimum order. In their 2019 paper, Filipovski, Ramos‐Rivera, and Jajcay present lower bounds on the orders of bipartite biregular ‐graphs, and call the graphs that attain these bounds bipartite biregular Moore cages. In our paper, we improve the lower bounds obtained in the above paper. Furthermore, in parallel with the well‐known classical results relating the existence of ‐regular Moore graphs of even girths , and 12 to the existence of projective planes, generalized quadrangles, and generalized hexagons, we prove that the existence of an ‐Steiner system yields the existence of a bipartite biregular ‐cage, and, vice versa, the existence of a bipartite biregular ‐cage whose order is equal to one of our lower bounds yields the existence of an ‐Steiner system. Moreover, with regard to the special case of Steiner triple systems, we completely solve the problem of determining the orders of ‐bipartite biregular cages for all integers . Considering girths higher than 6, we relate the existence of generalized polygons (quadrangles, hexagons, and octagons) to the existence of ‐, ‐, ‐, ‐ and ‐bipartite biregular cages, respectively. Using this connection, we also derive improved upper bounds for the orders of other classes of bipartite biregular cages of girths 8, 12, and 14.
Using social network analysis as a tool in action research
Authors: Paterson Susan , McInerney Elizabeth E. W. , Evans Scotney D.
Published: March 2022

The following paper presents case examples of one research team's use of social network analysis (SNA) with three different collaboratives in South Florida: (a) a Collective Impact initiative seeking to end youth homelessness, (b) a university collaborative of campus organizations working towards Black students' concerns, and (c) a movement network of local social justice organizations. The research team used SNA to assess the level of connectivity of three different community coalitions. While research questions were slightly different for each collaborative, each project asked about the frequency of communication between organizations to determine connectivity. Results vary between case examples. Both the Youth Homeless Collaboration and the Black Student Association used Gephi to analyze results, while The Community Partnership used R to measure network centrality. The paper concludes with a general discussion of challenges related to using SNA as an action research tool, as well as the role of power in organizational networks.
A model based on endorectal ultrasonography predicts lateral lymph node metastasis in low and middle rectal cancer
Authors: Yan Li , Weifeng Zhou , Qin Wang , Jinping Wang
Published: March 2022

Purpose

To investigate the risk factors for lymph node (LN) metastasis in low and middle rectal tumors, construct a predictive model and test the model's diagnostic efficacy.

Methods

The clinical and pathological data of 172 patients with rectal cancer confirmed by surgery were retrospectively evaluated, among whom 61 patients were finally included in this study. Patients were divided into positive groups and negative groups based on LN metastasis, and risk factors that might affect LN metastasis were analyzed. Finally, a risk predictive model was constructed based on the weights of each risk factor.

Results

Compared with pathology, the efficacy of diagnosing LN metastasis only according to conventional endorectal ultrasonography (ERUS) features of LN was not high, with sensitivity 67%, specificity 86%, positive predictive value 76%, negative predictive value 80%, and accuracy 79%. Univariate analysis showed that circumferential angle of the tumor, ultrasonic T‐ stage (UT stage), conventional ultrasound features diagnosis of LN metastasis, strain ratio (SR) of tumor were risk factors for LN metastasis, while vascular resistance index of rectal tumor was protective factor. Multivariate analysis showed that UT stage (OR = 7.188, p = 0.049), conventional ultrasound features diagnosis of LN metastasis (OR = 8.010, p = 0.025) and SR (OR = 5.022, p = 0.031) were independent risk factors for LN metastasis. These risk factors were included in logistic regression analysis and the model was established, Y = −7.3 + 1.9 X10 + 2.1 X11 + 1.6 X13 (Y = Logit[P], P: LN metastasis rate, X10: UT stage, X11: conventional ultrasound features diagnosis of LN metastasis, X13: SR). The receiver operating characteristic (ROC) curve was used to test the model's predictive efficacy, the area under the curve was 0.95, sensitivity: 95%, specificity: 87%. Hosmer–Lemeshow goodness of fit test showed X2 = 6.015, p = 0.65 (p > 0.05), indicating that the model had a high predictive value.

Conclusion

Evaluation of perirectal LN metastasis only based on conventional ERUS features of LN was not effective enough. UT stage of tumor, conventional ultrasound features diagnosis of LN metastasis and SR were independent risk factors for LN metastasis. The predictive model had good assessment efficacy and had certain clinical application value.
Saturated buffer design flow and performance in Illinois
Authors: Chandrasoma Janith , Christianson Reid , Cooke Richard Andrew , Davidson Paul C. , Lee DoKyoung , Christianson Laura
Published: March 2022

There are few peer‐reviewed studies documenting saturated buffer annual nitrate (NO3) removal or that have assessed the federal practice standard design criteria. Drainage flow, NO3, and dissolved reactive phosphorus (DRP) were monitored at three saturated buffers in Illinois, USA, for a combined 10 site‐years. Nitrate loss reduction averaged 48 ± 19% with removals of 3.5–25.2 kg NO3–N ha−1 annually. Median DRP concentrations at all sampling locations were at the analytical detection limit of 0.01 mg L−1. The current design paradigm (i.e., USDA practice standard) prescribes there should be no flow bypassing the saturated buffer at flow rates that are ≤5% of the peak drainage system flow rate. The drainage coefficient–based and Manning's equation‐based peak flow estimates were higher and lower, respectively, than the observed annual peaks in all years. This illustrated inherent uncertainty introduced early in the design process, which can be further compounded by dynamic in‐buffer hydrology. The percentage of the observed peak flow rate at which bypass initiated ranged across an order of magnitude between sites (4.4–8.1% of peak flow rate at one site and 42–49% of peak at another) despite the buffers providing relatively similar NO3 removal. Bypass at one site (SB2) was related to the concept of “antecedent buffer capacity filled,” which was defined as the 5‐d average water depth in the middle control structure chamber expressed as a relative percentage of the bypass stop log height. This design flow analysis serves as a call to further evaluate predictive relationships and design models for edge‐of‐field practices.
Wellness of hospitalists and hospital medicine advanced practice providers during the COVID‐19 pandemic, 2020–2021
Authors: Dugani Sagar B. , Fischer Karen M. , Schroeder Darrell R. , Geyer Holly L. , Maniaci Michael J. , Croghan Ivana T. , Kashani Daniel , Burton M. Caroline
Published: March 2022

Background

The early phase of the coronavirus disease 2019 (COVID‐19) pandemic had a negative impact on the wellness of hospitalists and hospital medicine advanced practice providers (APPs). However, the burden of the pandemic has evolved and the change in hospitalist and hospital medicine APP wellness is unknown.

Objective

To evaluate the longitudinal trend in wellness of hospitalists and hospital medicine APPs during the COVID‐19 pandemic and guide wellness interventions.

Design, Setting and Participants

Between May 4, 2020, and June 6, 2021, we administered three surveys to Internal Medicine hospitalists (physicians) and hospital medicine APPs (nurse practitioners and physician assistants) at 16 Mayo Clinic hospitals in four U.S. states.

Measurements

We evaluated the association of hospitalist and hospital medicine APP characteristics with PROMIS® measures of global wellbeing‐mental health, global wellbeing‐social activities and relationships, anxiety, social isolation, and emotional support, using logistic and linear regression models.

Results

The response rates were 52.2% (n=154/295; May 2020), 37.1% (n=111/299; October 2020) and 35.5% (n=114/321; May 2021). In mixed models that included hospitalist and hospital medicine APP characteristics and survey period, APPs, compared with physicians, had lower odds of top global wellbeing‐social activities and relationships (adjusted odds ratio 0.42 [0.22–0.82]; p = .01), whereas survey period showed no association. The survey period showed an independent association with higher anxiety (May 2020 vs. others) and higher social isolation (October 2020 vs. others), whereas profession showed no association. Concern about contracting COVID‐19 at work was significantly associated with lower odds of top global wellbeing‐mental health and global wellbeing‐social activities and relationships, and with higher anxiety and social isolation. Hospitalist and hospital medicine APP characteristics showed no association with levels of emotional support.

Conclusions

In this longitudinal assessment of hospitalists and hospital medicine APPs, concern about contracting COVID‐19 at work remained a determinant of wellness. The trend for global wellbeing, anxiety, and social isolation may guide wellness interventions.
Provider preferences for delivery of HIV care coordination services: results from a discrete choice experiment
Authors: Zimba Rebecca , Fong Chunki , Conte Madellena , Baim‐Lance Abigail , Robertson McKaylee , Carmona Jennifer , Gambone Gina , Nash Denis , Irvine Mary
Published: March 2022

Introduction

The PROMISE study was launched in 2018 to assess and document the implementation of changes to an existing HIV Care Coordination Programme (CCP) designed to address persistent disparities in care and treatment engagement among persons with HIV in New York City. We evaluated provider endorsement of features of the CCP to understand drivers of engagement with the programme.

Methods

We used a discrete choice experiment to measure provider endorsement of four CCP attributes, including: (1) how CCP helps with medication adherence, (2) how CCP helps with primary care appointments, (3) how CCP helps with issues other than primary care and (4) where CCP visits take place (visit location). Each attribute had three to four levels. Our primary outcomes were relative importance and part‐worth utilities, measures of preference for the levels of the four CCP program attributes, estimated using a hierarchical‐Bayesian multinomial logit model. All non‐medical providers in the core CCP positions of patient navigator, care coordinator and programme director or other administrator from each of the 25 revised CCP‐implementing agencies were eligible to participate.

Results

We received responses from 152 providers, 68% of whom identified as women, 49% identified as Latino/a, 34% identified as Black and 60% were 30–49 years old. Visit location (28.6%, 95% confidence interval [CI] 27.0–30.3%) had the highest relative importance, followed by how staff help with ART adherence (24.3%, 95% CI 22.4–26.1%), how staff help with issues other than primary care (24.2%, 95% CI 22.7–25.7%) and how staff help with primary care appointments (22.9%, 95% CI 21.7–24.1%). Within each of the above attributes, respectively, the levels with the highest part‐worth utilities were home visits 60 minutes from the program or agency (utility 19.9, 95% CI 10.7–29.0), directly observed therapy (utility 26.1, 95% CI 19.1–33.1), help with non‐HIV specialty medical care (utility 26.5, 95% CI 21.5–31.6) and reminding clients about and accompanying them to primary care appointments (utility 20.8, 95% CI 15.6–26.0).

Conclusions

Ongoing CCP refinements should account for how best to support and evaluate the intensive CCP components endorsed by providers in this study.
Men missing from the HIV care continuum in sub‐Saharan Africa: a meta‐analysis and meta‐synthesis
Authors: Nardell Maria F. , Adeoti Oluwatomi , Peters Carson , Kakuhikire Bernard , Govathson‐Mandimika Caroline , Long Lawrence , Pascoe Sophie , Tsai Alexander C. , Katz Ingrid T.
Published: March 2022

Introduction

Men are missing along the HIV care continuum. However, the estimated proportions of men in sub‐Saharan Africa meeting the UNAIDS 95‐95‐95 goals vary substantially between studies. We sought to estimate proportions of men meeting each of the 95‐95‐95 goals across studies in sub‐Saharan Africa, describe heterogeneity, and summarize qualitative evidence on factors influencing care engagement.

Methods

We systematically searched PubMed and Embase for peer‐reviewed articles published between 1 January 2014 and 16 October 2020. We included studies involving men ≥15 years old, with data from 2009 onward, reporting on at least one 95‐95‐95 goal in sub‐Saharan Africa. We estimated pooled proportions of men meeting these goals using DerSimonion‐Laird random effects models, stratifying by study population (e.g. studies focusing exclusively on men who have sex with men vs. studies that did not), facility setting (healthcare vs. community site), region (eastern/southern Africa vs. western/central Africa), outcome measurement (e.g. threshold for viral load suppression), median year of data collection (before vs. during or after 2017) and quality criteria. Data from qualitative studies exploring barriers to men's HIV care engagement were summarized using meta‐synthesis.

Results and discussion

We screened 14,896 studies and included 129 studies in the meta‐analysis, compiling data over the data collection period. Forty‐seven studies reported data on knowledge of serostatus, 43 studies reported on antiretroviral therapy use and 74 studies reported on viral suppression. Approximately half of men with HIV reported not knowing their status (0.49 [95% CI, 0.41–0.58; range, 0.09–0.97]) or not being on treatment (0.58 [95% CI, 0.51–0.65; range, 0.07–0.97]), while over three‐quarters of men achieved viral suppression on treatment (0.79 [95% CI, 0.77–0.81; range, 0.39–0.97]. Heterogeneity was high, with variation in estimates across study populations, settings and outcomes. The meta‐synthesis of 40 studies identified three primary domains in which men described risks associated with engagement in HIV care: perceived social norms, health system challenges and poverty.

Conclusions

Psychosocial and systems‐level interventions that change men's perceptions of social norms, improve trust in and accessibility of the health system, and address costs of accessing care are needed to better engage men, especially in HIV testing and treatment.
A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV‐negative women planning for or with pregnancy in rural Southwestern Uganda
Authors: Atukunda Esther Cathyln , Owembabazi Moran , Pratt Madeline Claire , Psaros Christina , Muyindike Winnie , Chitneni Pooja , Bwana Mwebesa Bosco , Bangsberg David , Haberer Jessica Elizabeth , Marrazzo Jeanne , Matthews Lynn Turner
Published: March 2022

Introduction

Antiretroviral pre‐exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high.

Methods

Between March 2018 and January 2019, in‐depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% and <80% adherence to PrEP doses measured by electronic pill cap, those who never initiated PrEP, and seven of their male partners. Content and dyadic analyses were conducted to identify emergent challenges and facilitators of PrEP use within individual and couple narratives.

Results

The median age for women was 33 years (IQR 28, 35), 97% felt likely to acquire HIV and 89% initiated PrEP. Individual‐level barriers included unwillingness to take daily pills while healthy, side effects and alcohol use. Women overcame these barriers through personal desires to have control over their HIV serostatus, produce HIV‐negative children and prevent HIV transmission within partnerships. Couple‐level barriers included nondisclosure, mistrust and gender‐based violence; facilitators included shared goals and perceived HIV protection, which improved communication, sexual intimacy and emotional support within partnerships through a self‐controlled method. Community‐level barriers included multi‐level stigma related to HIV, ARVs/PrEP and serodifference; facilitators included active peer, family or healthcare provider support as women aspired to safely meet socio‐cultural expectations to conceive and preserve serodifferent relationships. Confidence in PrEP effectiveness was promoted by positive peer experiences with PrEP and ongoing HIV testing.

Conclusions

Multi‐level forms of HIV‐, serodifference‐ and disclosure‐related stigma, side effects, pill burden, alcohol use, relationship dynamics, social, professional and partnership support towards adaptation and HIV risk reduction influence PrEP uptake and adherence among HIV‐negative women with plans for pregnancy in rural Southwestern Uganda. Confidence in PrEP, individually controlled HIV prevention and improved partnership communication and intimacy promoted PrEP adherence. Supporting individuals to overcome context‐specific barriers to PrEP use may be an important approach to improving uptake and prolonged use.
Gab2 promotes acute myeloid leukemia growth and migration through the SHP2-Erk-CREB signaling pathway
Authors: Gong Rui , Li Haoying , Liu Yaqi , Wang Yanyan , Ge Lu , Shi Liuzhi , Wu Guang , Lyu Jianxin , Gu Haihua , He Licai
Published: March 2022

Acute myeloid leukemia (AML) is a hematologic malignant disease largely affecting older adults with poor outcomes. Lack of effective targeted treatment is a major challenge in managing the disease in the clinic. Scaffolding adaptor Gab2 is amplified in a subset of AML. However, the causative role of Gab2 in AML remains to be explored. In this study, it was found that Gab2 was expressed at high levels in AML patient samples and AML cell lines. Experiments by knocking down Gab2 expression using shRNA showed that Gab2 promoted AML cell growth and migration in vitro and in vivo. Further studies using Gab2 mutants and pharmacological inhibitors revealed that Gab2 increased CREB phosphorylation via the SHP-2/Erk signaling pathway. CREB phosphorylation contributed to Gab2-induced cell migration by increasing MMP2 and MMP9 expression. This research indicates that high Gab2 expression promotes AML progression through the SHP2-Erk-CREB signaling pathway. CREB suppression may help treat AML with high Gab2 expression.
Development of a Piezoelectric Actuated Tactile Stimulation Device for Population Receptive Field Mapping in Human Somatosensory Cortex With fMRI
Authors: Wu Jinglong , Wang Chenyu , Wang Luyao , Wang Yutong , Yang Jiajia , Yan Tianyi , Suo Dingjie , Wang Li , Liu Xin , Zhang Jian
Published: March 2022

Background

Multichannel tactile stimulation devices is need to investigate human finger population receptive field (pRF) characteristics in the primary somatosensory cortex during functional magnetic resonance imaging (fMRI).

Purpose

To accurately characterize right‐hand somatosensory representation based on the Bayesian pRF model.

Study Type

Prospective.

Population

A water phantom and six healthy participants (four males, mean 23.8 years old).

Field Strength/Sequence

T1‐weighted magnetization‐prepared rapid gradient‐echo, T2*‐weighted echo planar imaging at 3 T.

Assessment

The piezoelectric actuated tactile stimulation device consisted of execution unit and control unit. The output performance of the device was measured by a laser displacement sensor. The effect of the device on images' signal‐to‐noise ratio (SNR) was measured by phantom experiments. The activation representation arrangement order, relative volumes, and receptive field size of the right hand were assessed during the along‐digits and cross‐digits paradigms.

Statistical Tests

The normality of the data was tested by the Shapiro–Wilk method. A paired‐sample t test was performed to test pRF characteristics for all digit pairings. The significance level was set to P = 0.05 (false discovery rate [FDR] correct).

Results

Percussive stimulation provided by the piezoelectric actuated tactile stimulator had a stable displacement (2.64 mm) over a wide range of vibration frequencies (0–30 Hz). The output delay of the device was 1 millisecond. The device did not affect the image's SNR (without the device: SNR = 138.24 ± 7.87, temporal SNR [TSNR] = 440.03 ± 52.08. With the device: SNR = 138.06 ± 8.44, TSNR = 438.52 ± 56.38. PSNR = 0.88, PTSNR = 0.46). Representations of right‐hand fingers showed the same arrangement order in both experiments (D1–D5 arranged along the central sulcus). However, the relative volumes of D3 showed significant differences in S1 (P = 0.003). Among four subareas, the relative volumes of D3 were significantly different in area 1 (P = 0.047).

Data Conclusion

This developed stimulator, through experimental verification, could play a role in pRF mapping exploration.

Level of Evidence

2

Technical Efficacy Stage

1
Internal Jugular Vein Geometry Under Multiple Inclination Angles with 3D Low‐Field MRI in Healthy Volunteers
Authors: van Zandwijk Jordy K. , Kuijer Koen M. , Stassen Chrit M. , ten Haken Bernard , Simonis Frank F.J.
Published: March 2022

Background

Cerebral venous pathways are subjected to geometrical and patency changes due to body position. The internal jugular veins (IJVs) are the main venous drainage pathway in supine position. Their patency and geometry should be evaluated under different body inclination angles over a three‐dimensional (3D) volume in the healthy situation to better understand pathological cases.

Purpose

To investigate whether positional changes in the body can affect the geometrical properties and patency of the venous system.

Study Type

Prospective.

Population

15 healthy volunteers, of which seven males and median age 22 years in a range of 19–59.

Field Strength/Sequence

A 0.25‐T tiltable MRI system was used to scan volunteers in 90° (sitting position), 69°, 45°, 21°, and 0° (supine position) in the transverse plane with the top at vertebra C2. A gradient echo sequence was used.

Assessment

Three observers assessed IJVs on patency and created automatic centerlines from which diameter and patency were analysed perpendicular to the vessel at every 4 mm starting at the level of C2.

Statistical Tests

A Student's t test was used to find statistical difference (p < 0.05) in average IJV diameters per inclination angle.

Results

The amount of fully collapsed IJVs increased from 33% to 93% (left IJV) and 14% to 80% (right IJV) when increasing the inclination angle from 0° to 90°. In both IJVs, the mean diameter (±SD) of the open vessels was significantly higher at 0° than 90° with 6.3 ± 0.5 mm vs. 4.4 ± 0.1 mm (left IJV) and 6.6 ± 0.6 mm vs. 4.3 ± 0.4 mm (right IJV).

Data Conclusion

Tiltable low‐field MRI can be used to assess IJV geometry and its associated venous pathways in 3D under multiple inclination angles. Next to a higher amount of collapsed vessels, the average diameter of noncollapsed vessels decreases with increasing inclination angles for both left and right IJVs.

Level of Evidence

2

Technical Efficacy Stage

1
Reverse genetics systems for SARS‐CoV‐2
Authors: Wang Wenhao , Peng Xiaoxue , Jin Yunyun , Pan Ji‐An , Guo Deyin
Published: March 2022

The ongoing pandemic of coronavirus disease 2019 (COVID‐19) has caused severe public health crises and heavy economic losses. Limited knowledge about this deadly virus impairs our capacity to set up a toolkit against it. Thus, more studies on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) biology are urgently needed. Reverse genetics systems, including viral infectious clones and replicons, are powerful platforms for viral research projects, spanning many aspects such as the rescues of wild‐type or mutant viral particles, the investigation of viral replication mechanism, the characterization of viral protein functions, and the studies on viral pathogenesis and antiviral drug development. The operations on viral infectious clones are strictly limited in the Biosafety Level 3 (BSL3) facilities, which are insufficient, especially during the pandemic. In contrast, the operation on the noninfectious replicon can be performed in Biosafety Level 2 (BSL2) facilities, which are widely available. After the outbreak of COVID‐19, many reverse genetics systems for SARS‐CoV‐2, including infectious clones and replicons are developed and given plenty of options for researchers to pick up according to the requirement of their research works. In this review, we summarize the available reverse genetics systems for SARS‐CoV‐2, by highlighting the features of these systems, and provide a quick guide for researchers, especially those without ample experience in operating viral reverse genetics systems.
Forecasts of MJO during DYNAMO in a coupled tropical channel model, Part I: Impact of parameterization schemes
Authors: Hu Yun , Wang Xiaochun , Luo Jing‐Jia , Wang Dongxiao , Yan Huiping , Yuan Chaoxia , Lin Xia
Published: March 2022

A coupled tropical channel model is developed to forecast the Madden–Julian Oscillation (MJO) event during the Dynamics of the MJO (DYNAMO) campaign period. Eight sets of 30‐day hindcast experiments are performed using different combinations of cumulus parameterization and planetary boundary layer (PBL) schemes. The results indicate that a well‐simulated mean state is a prerequisite for MJO forecast, and the model's ability to reproduce the mean state is sensitive to the parameterization schemes. The experiment with Tiedtke (TDK) cumulus parameterization and University of Washington (UW) PBL schemes can successfully predict the MJO event. Over the equatorial Indian Ocean, this experiment has a good representation of zonal sea surface temperature (SST) gradient and low‐level westerly wind, favouring a reasonable atmospheric circulation. As a result of boundary‐layer convergence in the eastern Indian Ocean, more water vapour is gathered in the low‐middle troposphere by updrafts, contributing to the PBL moistening ahead of the MJO convection and the eastward‐propagation of MJO precipitation. Further analysis reveals that the high cloud is accompanied by strong convection. A better simulation in tropical high cloud fraction helps trap the cloud radiation heating to warm middle‐upper troposphere, which promotes the MJO propagation. Our results suggest that the selection of proper parameterization schemes with a better‐simulated mean state is crucial to predicting the MJO event in the tropical channel model.