bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR-290 family maintains developmental potential by targeting p21 in mouse preimplantation embryos
Authors: Li Xiangnan , Liu Yueshi , Mu Qier , Tian Junliang , Yu Haiquan
Published: December 2021

The miR-290 family is a mouse-specific microRNA cluster, which maintains mouse embryonic stem cells (ESCs) pluripotency by increasing OCT3/4 and C-MYC expression. However, its functions in mouse preimplantation embryos remain unclear, especially during zygotic genome activation (ZGA). In this study, miR-290 family expression increased from the two-cell embryo stage through the blastocyst stage. Inhibition of miR-294-3p/5p did not affect ZGA initiation or embryo development, whereas pri-miR-290 knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived from pri-miR-290 knockdown blastocysts. To clarify the mechanism of action, 33 candidate miR-294-3p target genes were screened from three databases, and miR-294-3p directly targeted the 3′-untranslated region of Cdkn1a (p21) mRNA. Similar to pri-miR-290 knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 and pri-miR-290 partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targeting p21.
Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies
Authors: Xhima Kristiana , Markham-Coultes Kelly , Hahn Kofoed Rikke , Saragovi H Uri , Hynynen Kullervo , Aubert Isabelle
Published: December 2021

Early degeneration of basal forebrain cholinergic neurons contributes substantially to cognitive decline in Alzheimer’s disease. Evidence from preclinical models of neuronal injury and aging support a pivotal role for nerve growth factor (NGF) in neuroprotection, resilience, and cognitive function. However, whether NGF can provide therapeutic benefit in the presence of Alzheimer’s disease-related pathologies still unresolved. Perturbations in the NGF signalling system in Alzheimer’s disease may render neurons unable to benefit from NGF administration. Additionally, challenges related to brain delivery remain for clinical translation of NGF-based therapies in Alzheimer’s disease. To be safe and efficient, NGF-related agents should stimulate the NGF receptor, tropomyosin receptor kinase A (TrkA), avoid activation through the p75 neurotrophin receptor (p75NTR), and be delivered non-invasively to targeted brain areas using real-time monitoring. We addressed these limitations using MRI-guided focused ultrasound (MRIgFUS) to increase blood–brain barrier permeability locally and transiently, allowing an intravenously administered TrkA agonist that does not activate p75NTR, termed D3, to enter targeted brain areas. Here, we report the therapeutic potential of selective TrkA activation in a transgenic mouse model that recapitulates numerous Alzheimer’s disease-associated pathologies. Repeated MRIgFUS-mediated delivery of D3 (D3/FUS) improved cognitive function in the TgCRND8 model of Alzheimer’s disease. Mechanistically, D3/FUS treatment effectively attenuated cholinergic degeneration and promoted functional recovery. D3/FUS treatment also resulted in widespread reduction of brain amyloid pathology and dystrophic neurites surrounding amyloid plaques. Furthermore, D3/FUS markedly enhanced hippocampal neurogenesis in TgCRND8 mice, implicating TrkA agonism as a novel therapeutic target to promote neurogenesis in the context of Alzheimer’s disease-related pathology. Thus, this study provides evidence that selective TrkA agonism confers neuroprotection to effectively counteract Alzheimer’s disease-related vulnerability. Recent clinical trials demonstrate that non-invasive blood–brain barrier modulation using MRIgFUS is safe, feasible and reversible in Alzheimer’s disease patients. TrkA receptor agonists coupled with MRIgFUS delivery constitute a promising disease-modifying strategy to foster brain health and counteract cognitive decline in Alzheimer’s disease.
Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera From BNT162b2 or CoronaVac Vaccine Recipients
Authors: Lu Lu , Mok Bobo Wing Yee , Chen Lin Lei , Chan Jacky Man Chun , Tsang Owen Tak Yin , Lam Bosco Hoi Shiu , Chuang Vivien Wai Man , Chu Allen Wing Ho , Chan Wan Mui , Ip Jonathan Daniel , Chan Brian Pui Chun , Zhang Ruiqi , Yip Cyril Chik Yan , Cheng Vincent Chi Chung , Chan Kwok Hung , Jin Dong Yan , Hung Ivan Fan Ngai , Yuen Kwok Yung , Chen Honglin , To Kelvin Kai Wang
Published: December 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment.

Methods

Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay.

Results

The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7–39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K.

Conclusions

Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.
del Nido cardioplegia better preserves cardiac diastolic function but histidine–tryptophan–ketoglutarate is better for endothelial function
Authors: Xue Hong-Mei , Hou Hai-Tao , Sun Wen-Tao , Wang Shi-Fu , Guo Shan , Yang Qin , He Guo-Wei
Published: December 2021

OBJECTIVES

The effectiveness of myocardial protection of cardioplegia has been a matter of debate for decades. This study was designed to compare cardiac and endothelial protection of 3 clinically used cardioplegias: del Nido cardioplegia (DNC), histidine–tryptophan–ketoglutarate (HTK) and blood cardioplegia (BC) followed by HTK (BC + HTK) in a rat model of ischaemia/reperfusion (I/R).

METHODS

Sixty male Wistar rats were subjected to either 120 min of global ischaemia at 4°C followed by 90 min of reperfusion (I/R) at 37°C or no I/R (control) in a Langendorff apparatus and were randomly allocated to 5 groups: control, I/R, DNC, HTK and BC + HTK. Cold cardioplegia solutions were administered at doses of 20 ml/kg for DNC and HTK or 10 ml/kg for BC followed by HTK. Haemodynamic parameters were continuously recorded using an intraventricular balloon. The endothelium-dependent relaxation to acetylcholine was measured in the left anterior descending artery using a myograph. Protein expression of cardiac troponin T (cTnT) and creatine kinase MB was determined by western blot.

RESULTS

During reperfusion, HTK had higher left ventricular systolic pressure whereas DNC had lower left ventricular end-diastolic pressure, better left ventricular developed pressure and best +dp/dtmax and −dp/dtmax than the other 2 groups but the differences disappeared at the end of the reperfusion. HTK or BC + HTK preserves the acetylcholine-induced endothelium-dependent relaxation better than DNC (Emax = 48.2 ± 8.0% in DNC vs 75.0 ± 8.0% in HTK, P < 0.05; vs 96.9 ± 3.5% in BC + HTK, P < 0.001). The protein levels of cTnT and creatine kinase MB were downregulated in the 3 groups.

CONCLUSIONS

All 3 cardioplegias prevented myocardial damage against I/R injury at the end of reperfusion. DNC demonstrated better preserved diastolic function of the left ventricle whereas HTK or BC + HTK showed better preserved coronary endothelial function. These findings may suggest that currently no ‘perfect’ cardioplegia exists and that exploration for the ‘perfect’ cardioplegia is needed.
Infrared thoracoscopic pulmonary segmentectomy with intravenous indocyanine green administration using preoperative simulation
Authors: Igai Hitoshi , Matsuura Natsumi , Kamiyoshihara Mitsuhiro
Published: December 2021

Infrared thoracoscopy with intravenous indocyanine green administration is one of the useful methods to identify an appropriate intersegmental line during thoracoscopic pulmonary segmentectomy. In this procedure, we have introduced preoperative simulation to calculate the distance between the target tumour and intersegmental plane using Ziostation2 (Ziosoft, Tokyo, Japan) to ensure sufficient surgical margin without palpation. By using this preoperative simulation, we obtained sufficient surgical margin in a patient with a 16-mm part-solid nodular shadow undergoing infrared thoracoscopic upper division (S1–3) segmentectomy of left upper lobe with intravenous indocyanine green administration. The discrepancy between the virtual and the actual surgical margin was <10 mm. This preoperative simulation can help us obtain sufficient surgical margin without palpation of the tumour in infrared thoracoscopic segmentectomy.
How a pregnant woman’s relationships with her siblings relate to her mental health: a prenatal allocare perspective
Authors: Fox Molly , Wiley Kyle S
Published: December 2021

Background

In cooperatively breeding species, individuals may promote their inclusive fitness through allomothering. Humans exhibit some features of cooperative breeding, and previous studies have focused on allomothering by grandparents and juvenile siblings in the postnatal period. We hypothesize that a pregnant woman’s relationships with her siblings (offspring’s maternal aunts and uncles) are beneficial for maternal affect in ways that can enhance the siblings’ inclusive fitness. Maternal affect during pregnancy is a salient target of allocare given the detrimental effects of antepartum mood disorders on birth and infant outcomes.

Methodology

We test our hypotheses in a cohort of pregnant Latina women in Southern California (N = 201). Predictor variables of interest include number of siblings a participant has, if she has sisters, frequency of seeing siblings, and frequency of communication with siblings. Outcome variables measuring maternal affect include depression, state anxiety, pregnancy-related anxiety and perceived stress.

Results

Having at least one sister and greater frequency of communication with siblings were associated with fewer depressive symptoms during pregnancy. No significant associations were found between sibling variables and other measures of affect.

Conclusion and implications

Results suggest that how frequently you communicate with, and not how often you see, siblings could be protective against risk of antepartum depression. Sibling allomothering could impart effects through social–emotional support rather than instrumental support, as a strategy to benefit the prenatal environment in which future nieces and nephews develop. Allomothering may be particularly important in cultural contexts that value family relationships. Future studies should investigate other communities.
Measuring Hand Sensory Function and Force Control in Older Adults: Are Current Hand Assessment Tools Enough?
Authors: Logue Rachel N , Goldenkoff Elana R , Vesia Michael , Brown Susan H
Published: December 2021

Background

The ability to grasp and manipulate objects is essential for performing activities of daily living. However, there is limited information regarding age-related behavioral differences in hand sensorimotor function due, in part, to the lack of assessment tools capable of measuring subtle but important differences in hand function. The purpose of this study was to demonstrate performance differences in submaximal force control and tactile pattern recognition in healthy older adults using 2 custom-designed sensorimotor assessment tools.

Methods

Sensorimotor function was assessed in 13 healthy older adults (mean age 72.2 ± 5.5 years, range: 65–84 years) and 13 young adults (mean age 20 ± 1.4 years, range: 19–23 years). Clinical assessments included the Montreal Cognitive Assessment (MoCA), monofilament testing, maximum voluntary contraction (MVC), and Grooved Pegboard Test. Sensorimotor assessments included submaximal (5, 20% MVC) grip force step-tracking and tactile pattern recognition tasks.

Results

Clinical assessments revealed no or minimal group differences in MVC, monofilament thresholds, and MoCA. However, sensorimotor assessments showed that older adults took longer to discriminate tactile patterns and had poorer accuracy than young adults. Older adults also produced submaximal forces less smoothly than young adults at the 20% force level while greater variability in force maintenance was seen at 5% but not 20% MVC.

Conclusions

These results demonstrate the ability to integrate higher-order tactile information and control low grip forces is impaired in older adults despite no differences in grip strength or cognition. These findings underscore the need for more sensitive evaluation methods that focus on sensorimotor ability reflective of daily activities.
Housing Unit Type and Perceived Social Isolation Among Senior Housing Community Residents
Authors: Carbone Jason T , Clift Jennifer , Wyllie Tom , Smyth Amy
Published: December 2021

Background and Objectives

Social isolation, and its associated health implications, is an important issue for older adults in the United States. To date, there has been limited study of the pathways that connect these 2 factors. The present study expands on previous models by linking factors related to the built environment—in the form of housing unit type—to perceived social isolation among those living independently in dedicated senior housing.

Research Design and Methods

The causal inference technique of inverse probability weighting with regression adjustment was employed to assess the impact of living in a townhome-style unit, as opposed to in an apartment building, on self-reported perceived social isolation (N = 1,160).

Results

Individuals who lived in townhome-style housing reported a 10.4% lower probability of experiencing social isolation as a result of living in a townhome-style unit as opposed to an apartment building-style unit.

Discussion and Implications

The findings provide evidence for the conceptual model that characteristics specific to a given housing unit type may create conditions that exacerbate or buffer individuals from experiencing social isolation. This, in turn, has important implications for the targeting of interventions for social isolation. Policy considerations related to the type of affordable senior housing being built should also be informed by these findings. Additionally, future research should better explicate the role of housing unit type on mental and emotional health outcomes.
Risk factors for acute exacerbation of interstitial lung disease following lung cancer resection: a systematic review and meta-analysis
Authors: Hao Xiaohu , Hao Jianqi , Chen Cong , Peng Haoning , Zhang Jian , Cao Qi , Liu Lunxu
Published: December 2021

OBJECTIVES

The aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease (ILD) following lung cancer resection.

METHODS

We performed a literature screening on the databases including PubMed, Embase, Ovid MEDLINE® and the Web of Science for related studies published up to January 2021. Eligible studies were included and data on risk factors related to postoperative AE were extracted. All analyses were performed with random-effect model.

RESULTS

A total of 12 studies of 2655 lung cancer patients with ILD were included in this article. The meta-analysis indicated that male [odds ratios (ORs) = 1.78, 95% confidence interval (CI): 1.02–3.11, P = 0.041], usually interstitial pneumonia pattern on CT (OR = 1.52, 95% CI: 1.06–2.17, P = 0.021), Krebs von den Lungen-6 [standardized mean difference (SMD) = 0.50, 95% CI: 0.06–0.94, P = 0.027], white blood cell (SMD = 0.53, 95% CI: 0.12–0.93, P = 0.010), lactate dehydrogenase (SMD = 0.47, 95% CI: 0.04–0.90, P = 0.032), partial pressure of oxygen (weighted mean difference = −3.09, 95% CI: −5.99 to −0.19, P = 0.037), surgery procedure (OR = 2.31, 95% CI: 1.42–3.77, P < 0.001) and operation time (weighted mean difference = 28.26, 95% CI: 1.13–55.39, P = 0.041) were risk factors for AE of ILD following lung cancer resection.

CONCLUSIONS

We found that males, usually interstitial pneumonia pattern on CT, higher levels of Krebs von den Lungen-6, lactate dehydrogenase, white blood cell, lower partial pressure of oxygen, greater scope of operation and longer operation time were risk factors for AE of ILD following lung cancer resection. Patients with these risk factors should be more prudently selected for surgical treatment and be monitored more carefully after surgery.
Left ventricular assist device insertion and open abdominal aortic aneurysm repair in same admission for an end-stage heart failure patient
Authors: Wong Max K H , Ho Cally K L , Fan Katherine Y Y , Au Timmy W K
Published: December 2021

Patients suffering from end-stage heart failure also suffer from multiple cardiovascular comorbidities such as abdominal aortic aneurysm (AAA). Mechanical support with left ventricular assist device with open repair of AAA repair has rarely been reported in literature. The authors describe a 60-year-old male with end-stage heart failure and a symptomatic AAA with sequential left ventricular assist device insertion and open AAA repair with aortic cross-clamping.
Accepting the future as ever-changing: professionals’ sensemaking about artificial intelligence
Authors: Goto Masashi
Published: December 2021

This article examines how professionals leading the digitalization of professional service firms construct their views on new digital technologies such as artificial intelligence (AI) and the influence of such technologies on their future. This understudied question is important because such early-stage envisioning can significantly affect the later processes and outcomes of digitalization. A qualitative study was conducted, using interview and archival data, on a Big Four audit firm in Japan during the period 2017–9, when its taskforce considered applying AI to its core audit service. The contribution of this study is threefold. First, the findings expand our knowledge of prospective sensemaking by introducing a distinct mode of viewing the future that accepts the future as ever-changing as a means of coping with high uncertainty. Second, this study demonstrates the understudied link between institutions and sensemaking by showing how professionals’ embeddedness in their professional institution sets the focus of their sensemaking on the elements that support the institution. Third, these insights add to our knowledge of digitalization and professions by suggesting the potential high variability of professionals’ strategies regarding digitalization due to their continuous updating of their view of the future, as well as the inherent antinomy of digitalization for established professions due to their advantaged but constrained position regarding digitalization.
Primary cutaneous B-cell lymphoma arising from an inguinal hernioplasty scar
Authors: Vaz-Pereira Ricardo , Moreira Herculano , Monteiro Ana , Melo Ana , Leal Clara , Vieira Bruno , Freitas Francisca , Marques Carolina , Pinto-de-Sousa João
Published: December 2021

The primary cutaneous B-cell lymphoma (PCBCL) is a rare neoplasm. It is believed that antigenic stimulation and chronic inflammation can be the basis of pathogenesis. Here, we report a case that to our knowledge is the first patient with a presentation of a PCBCL arising from a surgical scar, in particular, an inguinal hernioplasty. The case reminds us of the importance of raising clinical suspicion for malignant neoplasms in surgical scars, in particular, after mesh placement. MeSH terms: ‘lymphoma, large b-cell, diffuse’, ‘skin’ and ‘cicatrix’.
The Public Health Approach to the Worsening Opioid Crisis in the United States Calls for Harm Reduction Strategies to Mitigate the Harm From Opioid Addiction and Overdose Deaths
Authors: Yeo Yvon , Johnson Rosemary , Heng Christine
Published: December 2021

The opioid crisis has devastated the U.S. more than any other country, and the epidemic is getting worse. While opioid prescriptions have decreased by more than 40% from its peak in 2010, unfortunately, opioid-related overdose deaths have not declined but continued to increase. With greater scrutiny on prescription opioids, many users switched to the cheaper and more readily available heroin that drove up heroin-related overdose deaths from 2010 to peak in 2016, being overtaken by the spike in synthetic opioid (mostly fentanyl)-related overdose deaths. The surge in fentanyl-related overdose deaths since 2013 is alarming as fentanyl is more potent and deadly. One thing is certain the opioid crisis is not improving but has become dire with the surge in fentanyl-related overdose deaths. Evidence-based strategies have to be implemented in the U.S. to control this epidemic before it destroys more lives. Other countries, including European countries and Canada, have invested more in harm reduction strategies than the U.S. even though they (especially Europe) do not face anywhere near the level of crisis as the U.S. In the long-run, upstream measures (tackling the social determinants of health) are more effective public health strategies to control the epidemic. In the meantime, however, harm reduction strategies have to be employed to mitigate the harm from addiction and overdose deaths.
Trends in Surgical Case Volume During Pacific Partnership Missions Onboard USNS Mercy
Authors: Sykes Alicia G , Brill Jason B , Wallace James D , Lee Clara , Lewis Paul R , Henry Marion C , Christman Matthew S , Casey Kevin M , Bickler Stephen W , Ignacio Romeo C
Published: December 2021

Introduction

Since 2006, the U.S. Navy has conducted six Pacific Partnership (PP) missions throughout Southeast Asia on board the U.S. Naval Ship Mercy (T-AH 19). This study describes trends in overall and surgical specialty operative volumes to better understand the burden of surgical disease treated during these humanitarian and civic assistance (HCA) operations. This information can assist medical planners and surgical leaders involved in future humanitarian missions.

Materials and Methods

Following approval from the Naval Medical Center San Diego Institutional Review Board, a retrospective review of surgical case data was performed for the six PP missions from 2006 to 2018. Data collected included patient demographics, Current Procedural Terminology codes, and surgical specialty. The primary outcome was surgical case volume per specialty. Secondary outcomes included surgical staffing per mission and overall trends in operative volume.

Results

A total of 3,826 operative procedures were performed during the study period. Mission years in which case volume for both general surgery and ophthalmology were below their respective medians were associated with the least total surgical services to host nations (HNs). The number of active duty Navy surgeons varied with each mission; however, the staffing for a PP mission generally included at least two general surgeons, one ophthalmologist, one plastic surgeon, one pediatric surgeon, one orthopedic surgeon, one otolaryngologist, one oral surgeon, one urologist, and one obstetrician–gynecologist. Case volume per surgeon was highest in 2006 (50 cases per surgeon) and decreased after 2006, reaching an all-time low during the 2018 PP mission (10 cases per surgeon). Pediatric surgery and plastic surgery had the highest average case volumes per surgeon at 58 and 46 cases per surgeon, respectively, while oromaxillofacial surgery and neurosurgery had the lowest average case volumes per surgeon at 9 and 14 cases per surgeon, respectively.

Conclusions

Operative volume on military HCA missions is greatly influenced by the priorities of the HN, the mission focus, the number of individuals from the HN that present for screening, and the availability of personnel and resources available on the hospital ship. Future mission planning should optimize general surgery and ophthalmology staffing and essential equipment, as total mission case volumes were highly dependent upon the productivity of these two specialties. Careful determination of the surgical needs of HNs should serve as a guide for the selection of subspecialists to maximize effectiveness in future military HCA missions.
Racial Disparities in the Military Health System: A Framework Synthesis
Authors: Koehlmoos Tracey Pérez , Korona-Bailey Jessica , Janvrin Miranda Lynn , Madsen Cathaleen
Published: December 2021

Introduction

Racial disparities in health care are a well-documented phenomenon in the USA. Universal insurance has been suggested as a solution to mitigate these disparities. We examined race-based disparities in the Military Health System (MHS) by constructing and analyzing a framework of existing studies that measured disparities between direct care (care provided by military treatment facilities) and private sector care (care provided by civilian health care facilities).

Materials and Methods

We conducted a framework synthesis on 77 manuscripts published in partnership with the Comparative Effectiveness and Provider-Induced Demand Collaboration Project that use MHS electronic health record data to present an overview of racial disparities assessed for multiple treatment interventions in a nationally representative, universally insured population.

Results

We identified 32 studies assessing racial disparities in areas of surgery, trauma, opioid prescription and usage, women’s health, and others. Racial disparities were mitigated in postoperative complications, trauma care, and cancer screenings but persisted in diabetes readmissions, opioid usage, and minimally invasive women’s health procedures.

Conclusion

Universal coverage mitigates many, but not all, racial disparities in health care. An examination of a broader range of interventions, a closer look at variation in care provided by civilian facilities, and a look at the quality of care by race provide further opportunities for research.
The Perceptual Awareness Scale—recent controversies and debates
Authors: Overgaard Morten , Sandberg Kristian
Published: December 2021

Accurate insight into subjective experience is crucial for the science of consciousness. The Perceptual Awareness Scale (PAS) was created in 2004 as a method for obtaining precise introspective reports for participants in research projects, and since then, the scale has become increasingly popular. This does not mean, of course, that no critiques have been voiced. Here, we briefly recapitulate our main thoughts on the intended PAS usage and the findings of the first decade, and we update this with the latest empirical and theoretical developments. We focus specifically on findings with relevance to whether consciousness is gradual or all-or-none phenomenon, to what should be considered conscious/unconscious, and to whether PAS is preferable to alternative measures of awareness. We respond in detail to some recent, selected articles.
Representational ‘touch’ and modulatory ‘retouch’—two necessary neurobiological processes in thalamocortical interaction for conscious experience
Authors: Bachmann Talis
Published: December 2021

Theories of consciousness using neurobiological data or being influenced by these data have been focused either on states of consciousness or contents of consciousness. These theories have occasionally used evidence from psychophysical phenomena where conscious experience is a dependent experimental variable. However, systematic catalog of many such relevant phenomena has not been offered in terms of these theories. In the perceptual retouch theory of thalamocortical interaction, recently developed to become a blend with the dendritic integration theory, consciousness states and contents of consciousness are explained by the same mechanism. This general-purpose mechanism has modulation of the cortical layer-5 pyramidal neurons that represent contents of consciousness as its core. As a surplus, many experimental psychophysical phenomena of conscious perception can be explained by the workings of this mechanism. Historical origins and current views inherent in this theory are presented and reviewed.
Origins of biallelic inactivation of NF2 in neurofibromatosis type 2
Authors: Xue Lu , He Weiwei , Zhang Yi , Wang Zhigang , Chen Hongsai , Chen Zhe , Zhu Weidong , Liu Dongmei , Jia Huan , Jiang Yi , Wang Zhaoyan , Wu Hao
Published: December 2021

Background

Elucidating the mechanism by which biallelic inactivation evolved could provide a mechanistic understanding for NF2 tumorigenesis and also a rationale for clinical management.

Methods

A cohort of 60 NF2 patients was recruited. Next-generation sequencing of tumor and paired control samples was used to explore how NF2 mutations evolve in determining the clinical phenotypes.

Results

In total, 60 blood samples (one from each patient) and 61 (from 35 patients) NF2-associated tumors were collected. Next-generation sequencing of the blood samples detected “first hit” NF2 mutation in 35/60 donors (58.3%), 82.9% of which (29/35) bear heterozygous germline mutations, and 17.1% (6/35) of which are mosaics with variable allelic frequency (VAF). While a number of NF2 patients were found without germline mutation, most (57/61, 93.4%) NF2-associated tumors were identified with NF2 somatic mutation. We calculated the correlation between the onset latency of mosaic and germline NF2 allele carriers with the mosaicism VAF. The mosaicism VAF is negatively and linearly correlated to clinical symptom onset latency (R2 = 0.3677, P = .00351), suggesting biallelic inactivation probability is a linear function of “first hit” prevalence in the body. The second NF2 somatic mutation occurrence time positively correlates with the onset of clinical symptoms (R2 = 0.4151, P = .02633), suggesting tumor growth is linearly proportional to the time after biallelic inactivation.

Conclusions

Our results suggested that biallelic inactivation of NF2 evolved through neutral drift and preexisting first hit NF2 allele determines certain aspects of the clinical symptoms. Genetic diagnosis should be included in the diagnostic criteria and treatment consideration of NF2.
Triage of Persons With Tuberculosis Symptoms Using Artificial Intelligence–Based Chest Radiograph Interpretation: A Cost-Effectiveness Analysis
Authors: Nsengiyumva Ntwali Placide , Hussain Hamidah , Oxlade Olivia , Majidulla Arman , Nazish Ahsana , Khan Aamir J , Menzies Dick , Ahmad Khan Faiz , Schwartzman Kevin
Published: December 2021

Background

In settings without access to rapid expert radiographic interpretation, artificial intelligence (AI)–based chest radiograph (CXR) analysis can triage persons presenting with possible tuberculosis (TB) symptoms, to identify those who require additional microbiological testing. However, there is limited evidence of the cost-effectiveness of this technology as a triage tool.

Methods

A decision analysis model was developed to evaluate the cost-effectiveness of triage strategies with AI-based CXR analysis for patients presenting with symptoms suggestive of pulmonary TB in Karachi, Pakistan. These strategies were compared to the current standard of care using microbiological testing with smear microscopy or GeneXpert, without prior triage. Positive triage CXRs were considered to improve referral success for microbiologic testing, from 91% to 100% for eligible persons. Software diagnostic accuracy was based on a prospective field study in Karachi. Other inputs were obtained from the Pakistan TB Program. The analysis was conducted from the healthcare provider perspective, and costs were expressed in 2020 US dollars.

Results

Compared to upfront smear microscopy for all persons with presumptive TB, triage strategies with AI-based CXR analysis were projected to lower costs by 19%, from $23233 per 1000 persons, and avert 3%–4% disability-adjusted life-years (DALYs), from 372 DALYs. Compared to upfront GeneXpert, AI-based triage strategies lowered projected costs by 37%, from $34346 and averted 4% additional DALYs, from 369 DALYs. Reinforced follow-up for persons with positive triage CXRs but negative microbiologic tests was particularly cost-effective.

Conclusions

In lower-resource settings, the addition of AI-based CXR triage before microbiologic testing for persons with possible TB symptoms can reduce costs, avert additional DALYs, and improve TB detection.
The Leningrad School of Neo-Modernism
Authors: von Zitzewitz Josephine
Published: December 2021

Leningrad was the centre of a boom in samizdat poetry in the 1970s and home to poets such as Viktor Krivulin, Elena Shvarts, Oleg Okhapkin, Aleksandr Mironov, Sergei Stratanovskii, and their older contemporary, Leonid Aronzon. Their work is now recognized as one of the key currents in Russian postmodernism. This article surveys the points that unite the poets of this current, with particular emphasis on their intertextual relationship with Modernist poets, the understanding of the role of the poet, the significance of religious imagery, and the unofficial seminars and journals that fostered and promoted the extraordinary literary creativity of Leningrad’s unofficial culture.
The Ethics of Human-Robot Interaction and Traditional Moral Theories
Authors: Nyholm Sven
Published: December 2021

The rapid introduction of different kinds of robots and other machines with artificial intelligence into different domains of life raises the question of whether robots can be moral agents and moral patients. In other words, can robots perform moral actions? Can robots be on the receiving end of moral actions? To explore these questions, this chapter relates the new area of the ethics of human–robot interaction to traditional ethical theories such as utilitarianism, Kantian ethics, and virtue ethics. These theories were developed with the assumption that the paradigmatic examples of moral agents and moral patients are human beings. As this chapter argues, this creates challenges for anybody who wishes to extend the traditional ethical theories to new questions of whether robots can be moral agents and/or moral patients.
Third data release of the Hyper Suprime-Cam Subaru Strategic Program
Authors: Aihara Hiroaki , AlSayyad Yusra , Ando Makoto , Armstrong Robert , Bosch James , Egami Eiichi , Furusawa Hisanori , Furusawa Junko , Harasawa Sumiko , Harikane Yuichi , Hsieh Bau-Ching , Ikeda Hiroyuki , Ito Kei , Iwata Ikuru , Kodama Tadayuki , Koike Michitaro , Kokubo Mitsuru , Komiyama Yutaka , Li Xiangchong , Liang Yongming , Lin Yen-Ting , Lupton Robert H , Lust Nate B , MacArthur Lauren A , Mawatari Ken , Mineo Sogo , Miyatake Hironao , Miyazaki Satoshi , More Surhud , Morishima Takahiro , Murayama Hitoshi , Nakajima Kimihiko , Nakata Fumiaki , Nishizawa Atsushi J , Oguri Masamune , Okabe Nobuhiro , Okura Yuki , Ono Yoshiaki , Osato Ken , Ouchi Masami , Pan Yen-Chen , Plazas Malagón Andrés A , Price Paul A , Reed Sophie L , Rykoff Eli S , Shibuya Takatoshi , Simunovic Mirko , Strauss Michael A , Sugimori Kanako , Suto Yasushi , Suzuki Nao , Takada Masahiro , Takagi Yuhei , Takata Tadafumi , Takita Satoshi , Tanaka Masayuki , Tang Shenli , Taranu Dan S , Terai Tsuyoshi , Toba Yoshiki , Turner Edwin L , Uchiyama Hisakazu , Vijarnwannaluk Bovornpratch , Waters Christopher Z , Yamada Yoshihiko , Yamamoto Naoaki , Yamashita Takuji
Published: December 2021

This paper presents the third data release of the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP), a wide-field multi-band imaging survey with the Subaru 8.2 m telescope. HSC-SSP has three survey layers (Wide, Deep, and UltraDeep) with different area coverages and depths, designed to address a wide array of astrophysical questions. This third release from HSC-SSP includes data from 278 nights of observing time and covers about 670 deg2 in all five broad-band filters (grizy) at the full depth (∼26 mag at 5σ depending on filter) in the Wide layer. If we include partially observed areas, the release covers 1470 deg2. The Deep and UltraDeep layers have $\sim\! 80\%$ of the originally planned integration times, and are considered done, as we have slightly changed the observing strategy in order to compensate for various time losses. There are a number of updates in the image processing pipeline. Of particular importance is the change in the sky subtraction algorithm; we subtract the sky on small scales before the detection and measurement stages, which has significantly reduced the number of false detections. Thanks to this and other updates, the overall quality of the processed data has improved since the previous release. However, there are limitations in the data (for example, the pipeline is not optimized for crowded fields), and we encourage the user to check the quality assurance plots as well as a list of known issues before exploiting the data. The data release website is 〈https://hsc-release.mtk.nao.ac.jp〉.
TOR promotes guard cell starch degradation by regulating the activity of β-AMYLASE1 in Arabidopsis
Authors: Han Chao , Hua Wenbo , Li Jinge , Qiao Yan , Yao Lianmei , Hao Wei , Li Ruizi , Fan Min , De Jaeger Geert , Yang Wenqiang , Bai Ming-Yi
Published: December 2021

Starch is the main energy storage carbohydrate in plants and serves as an essential carbon storage molecule for plant metabolism and growth under changing environmental conditions. The TARGET of RAPAMYCIN (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrient, hormone, and stress signaling to regulate growth in all eukaryotes. Here, we demonstrate that TOR promotes guard cell starch degradation and induces stomatal opening in Arabidopsis thaliana. Starvation caused by plants growing under short photoperiod or low light photon irradiance, as well as inactivation of TOR, impaired guard cell starch degradation and stomatal opening. Sugar and TOR induce the accumulation of β-AMYLASE1 (BAM1), which is responsible for starch degradation in guard cells. The plant steroid hormone brassinosteroid and transcription factor BRASSINAZOLE-RESISTANT1 play crucial roles in sugar-promoted expression of BAM1. Furthermore, sugar supply induced BAM1 accumulation, but TOR inactivation led to BAM1 degradation, and the effects of TOR inactivation on BAM1 degradation were abolished by the inhibition of autophagy and proteasome pathways or by phospho-mimicking mutation of BAM1 at serine-31. Such regulation of BAM1 activity by sugar–TOR signaling allows carbon availability to regulate guard cell starch metabolism and stomatal movement, ensuring optimal photosynthesis efficiency of plants.
Half-maximal extended Drinfel’d algebras
Authors: Sakatani Yuho
Published: December 2021

The extended Drinfel’d algebra (ExDA) is the underlying symmetry of non-Abelian duality in the low-energy effective theory of string theory. Non-Abelian U-dualities in maximal supergravities have been studied well, but there has been no study on non-Abelian dualities in half-maximal supergravities. We construct the ExDA for half-maximal supergravities in d ≥ 4. We also find an extension of the homogeneous classical Yang–Baxter equation in these theories.
How Important is Affiliation Between Mutual Funds and Distributors for Fund Flows?
Authors: Florentsen Bjarne , Nielsson Ulf , Raahauge Peter , Rangvid Jesper
Published: December 2021

We quantify the importance to mutual fund flows of affiliation between funds and their distributors. Bank failures create exogenous variation in retail customers’ exposure to bank-affiliated mutual funds. When a bank fails, its customers are moved to other banks that distribute their own affiliated mutual funds. Following such exogeneous bank shifts, customers sell their fund holdings and replace them with funds affiliated with their new banks. Customers react sequentially over time. After 4 years, a third of customers’ investments have been reallocated. In spite of large reallocations, investors do not end up with better-performing fund portfolios.
Update on gout management: what is old and what is new
Authors: Afinogenova Yuliya , Danve Abhijeet , Neogi Tuhina
Published: December 2021

Purpose of review

The global burden of gout is rising, as are the prevalence of associated comorbidities, all-cause mortality and societal costs. In this review, we discuss recent advances in epidemiology and treatment strategies for gout.

Recent findings

Genetic factors and obesity are prominent contributors to hyperuricemia and gout, while dietary factors contribute to less variance in serum urate, though can still have some contribution to population attributable risk. A consensus statement by the Gout, Hyperuricemia and Crystal-Associated Disease Network outlined appropriate terminology regarding gout, which will aid in communication about various aspects of the disease. The 2020 American College of Rheumatology gout guideline offers comprehensive evidence-based recommendations for the management of hyperuricemia using urate-lowering therapy, prophylaxis when initiating urate-lowering therapy, treatment of gout flare and adjunctive management strategies. There is improved understanding of risk factors for allopurinol hypersensitivity syndrome and well tolerated use of allopurinol in chronic kidney disease. Trial data have provided new insights regarding cardiovascular risk with febuxostat. Several new drug therapies are being tested for both urate-lowering efficacy and gout flare management.

Although there have been significant advances in understanding of risk factors and treatment approaches, gout remains suboptimally managed. There is substantial need for improving gout management efforts and gout education among patients and clinicians.
DNA Methylation and mRNA Expression of OX40 (TNFRSF4) and GITR (TNFRSF18, AITR) in Head and Neck Squamous Cell Carcinoma Correlates With HPV Status, Mutational Load, an Interferon-γ Signature, Signatures of Immune Infiltrates, and Survival
Authors: Loick Sophia M. , Fröhlich Anne , Gabrielpillai Jennis , Franzen Alina , Vogt Timo J. , Dietrich Jörn , Wiek Constanze , Scheckenbach Kathrin , Strieth Sebastian , Landsberg Jennifer , Dietrich Dimo
Published: December 2021

The tumor necrosis factor receptor superfamily members 4 (TNFRSF4, OX40) and 18 (TNFRSF18, GITR, AITR) are under investigation as targets for immunotherapy of various cancers, including head and neck squamous cell carcinomas. Understanding the regulation of OX40 and GITR, particularly on an epigenetic level, might help to develop companion predictive biomarkers. We conducted broad correlation analyses of DNA methylation of 46 CpG sites within the GITR/OX40 gene locus in head and neck squamous cell carcinomas and normal adjacent tissues provided by The Cancer Genome Atlas (TCGA) Research Network. We analyzed methylation levels with regard to transcriptional gene activity (mRNA expression), human papillomavirus (HPV) infection, differential methylation between tumors and normal adjacent tissues, signatures of immune cell infiltrates, an interferon-γ signature, mutational load, and overall survival. Moreover, we investigated methylation levels in HPV-positive and HPV-negative cell lines and in isolated monocytes, granulocytes, CD8+ and CD4+ T cells, and B cells from peripheral blood from healthy donors. Our results revealed a complex and sequence-contextual methylation pattern in accordance with features of epigenetic regulated genes. We detected significant methylation differences between normal adjacent and tumor tissues, between HPV-positive and HPV-negative tumors, between tumor and immune cells, and significant correlations between methylation and mRNA expression. We further found significant correlations of CpG methylation with overall survival, signatures of immune cell infiltrates, an interferon-γ signature, and mutational load. Our study provides a framework to prospectively test specific CpG sites as biomarkers, in particular in the context of immunotherapies.
Differential Mortality Risks Associated With PM2.5 Components
Authors: Masselot Pierre , Sera Francesco , Schneider Rochelle , Kan Haidong , Lavigne Éric , Stafoggia Massimo , Tobias Aurelio , Chen Hong , Burnett Richard T. , Schwartz Joel , Zanobetti Antonella , Bell Michelle L. , Chen Bing-Yu , Guo Yue-Liang Leon , Ragettli Martina S. , Vicedo-Cabrera Ana Maria , Åström Christofer , Forsberg Bertil , Íñiguez Carmen , Garland Rebecca M. , Scovronick Noah , Madureira Joana , Nunes Baltazar , De la Cruz Valencia César , Hurtado Diaz Magali , Honda Yasushi , Hashizume Masahiro , Ng Chris Fook Cheng , Samoli Evangelia , Katsouyanni Klea , Schneider Alexandra , Breitner Susanne , Ryti Niilo R.I. , Jaakkola Jouni J.K. , Maasikmets Marek , Orru Hans , Guo Yuming , Valdés Ortega Nicolás , Matus Correa Patricia , Tong Shilu , Gasparrini Antonio
Published: December 2021

Background:

The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality.

Methods:

We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators.

Results:

We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4
+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3
−) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk.

Conclusions:

These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.