bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing approximate shell-model wavefunctions by eigenvector continuation
Authors: Yoshida Sota , Shimizu Noritaka
Published: March 2022

Shell-model calculations play a key role in elucidating various properties of nuclei. In general, those studies require a huge number of calculations to be repeated for parameter calibration and quantifying uncertainties. To reduce the computational burden, we propose a new workflow of shell-model calculations using a method called eigenvector continuation (EC). It enables us to efficiently approximate the eigenpairs under a given Hamiltonian by previously sampled eigenvectors. We demonstrate the validity of EC as an emulator of the valence shell-model, including first application of EC to electromagnetic transition matrix elements. Furthermore, we propose a new usage of EC: preprocessing, in which we start the Lanczos iterations from the approximate eigenvectors, and demonstrate that this can accelerate subsequent research cycles. With the aid of the EC, the eigenvectors obtained during the parameter optimization are not necessarily to be discarded, even if their eigenvalues are far from the experimental data. Those eigenvectors can become accumulated knowledge.
The Goldbach Conjecture With Summands In Arithmetic Progressions
Authors: Salmensuu Juho
Published: March 2022

We prove that, for almost all $r \leq N^{1/2}/\log^{O(1)}N$, for any given $b_1 \ (\mathrm{mod}\ r)$ with $(b_1, r) = 1$, and for almost all $b_2 \ (\mathrm{mod}\ r)$ with $(b_2, r) = 1$, we have that almost all natural numbers $2n \leq N$ with $2n \equiv b_1 + b_2 \ (\mathrm{mod}\ r)$ can be written as the sum of two prime numbers $2n = p_1 + p_2$, where $p_1 \equiv b_1 \ (\mathrm{mod}\ r)$ and $p_2 \equiv b_2 \ (\mathrm{mod}\ r)$. This improves the previous result which required $r \leq N^{1/3}/\log^{O(1)}N$ instead of $r \leq N^{1/2}/\log^{O(1)}N$. We also improve some other results concerning variations of the problem.
Advertising Arbitrage
Authors: Kovbasyuk Sergey , Pagano Marco
Published: March 2022

An arbitrageur with short investment horizon gains from accelerating price discovery by advertising his private information. However, advertising many assets may overload investors’ attention, reducing the number of informed traders per asset, and slowing price discovery. So the arbitrageur optimally concentrates advertising on just a few assets, unless his trades have significant price impact. The arbitrageur’s gain from advertising is increasing in the assets’ mispricing and in the precision of his private information, and is decreasing in its complexity. If several arbitrageurs have private information, inefficient equilibria can arise, where substantial mispricing persists or investors’ attention is overloaded.
EXPERIMENTAL STUDIES AT THE IES ON THE BIOLOGICAL EFFECTS OF CHRONIC LOW DOSE-RATE RADIATION EXPOSURE IN MICE
Authors: Tanaka Ignacia Braga
Published: March 2022

Research in the Department of Radiobiology at the Institute for Environmental Sciences (IES) has focused mainly on the biological effects of long-term low dose-rate radiation exposure on mice since its establishment 30 y ago. The IES has exposed thousands of mice of various strains, to gamma-rays, mostly chronically, at low dose-rates of 0.05, 1, 20 or 100 mGy/d, at medium dose-rates of 200 or 400 mGy/d or at acute high dose-rates of 0.7–0.9 Gy/min. The dose-rate 0.05 mGy/d is comparable with the dose limit for radiation workers of 100 mSv/5 y. The results will be presented based on the parameters examined at various endpoints such as life span, neoplasm (cancer incidence), chromosome aberrations frequencies, alterations in mRNA levels, tumour transplantability and developmental abnormalities after in utero exposures. The results from research collaborations with universities and institutions both domestic (within Japan) and international will be presented. Lastly, an outline of experiments (e.g. juvenile exposure, low dose tritium exposures) and projects (e.g. radiobiology archives) currently in progress and future research perspectives will be described.
The Susceptibility of Legal Institutions: “Texts” and Contexts of the Transplanted IP Laws in China
Authors: He Qiaoling
Published: March 2022

Previous studies often attribute the poor enforcement of intellectual property rights (IPR) law in non-Western countries to environmental constraints, including social, political, or cultural factors. This article tries to reorient our focus to two intrinsic characteristics of legal rights appertaining to their social forms: the intangibility of the constructed legal object and the scope of contradictions among legal subjects. Based on 85 in-depth interviews from six IP-intensive industries in China, I propose a theoretical framework for combining the “textual” and contextual dimensions of studying legal transplants – the susceptibility of law. I argue that the intrinsic qualities of the IP legal concept imply a sizable gray space, making it difficult to interpret, hard to enforce, and thus more susceptible to specific contextual influences. The country-level contextual environment does not provide adequate technique, legitimacy, and experience to effectively enforce IPRs in general, yet some industries may benefit from a set of sub-contexts that provide compensatory support through product-embedded standardizations or network-embedded norms. Although these sub-contexts are not enough to produce a robust IPR regime as in the West, they do generate pockets of effectiveness, allowing industries to muddle through and profit, and an otherwise foreign institution gradually to take root.
Mechanism of kidney injury induced by cisplatin
Authors: Huang Guochen , Zhang Qian , Xu Chunming , Chen Long , Zhang Hongxia
Published: March 2022

Cisplatin is a common metal platinum complex. The platinum atom in the molecule is of great significance to its antitumor effect. Clinically, it can show curative effect on a variety of solid tumors. However, cisplatin has certain adverse effects in treatment, one among which is acute renal injury (AKI). Except for the nuclear DNA damage caused by cisplatin, damage of organelles, and cytoplasm also contribute to side effects. Endoplasmic reticulum stress, mitochondrial apoptosis pathway or cascade reaction caused by complement and caspase protein also play important roles in cisplatin induced renal injury. Therefore, the damage studies of organelles and cytoplasm are also necessary for exploring adverse effects of cisplatin. This paper reviews the damage of endoplasmic reticulum, mitochondria, and indirect DNA apoptosis pathways induced by cisplatin. It also explains in detail why cisplatin is easy to cause kidney damage. Deep understanding of such interactions could be helpful to exploit better drugs which would minimize kidney injury and maximize anti-tumor effects of cisplatin.
Worldwide Population Structure of the Coffee Rust Fungus Hemileia vastatrix Is Strongly Shaped by Local Adaptation and Breeding History
Authors: Rodrigues Ana Sofia B. , Silva Diogo Nuno , Várzea Vitor , Paulo Octávio S. , Batista Dora
Published: March 2022

The devastating disease coffee leaf rust, caused by Hemileia vastatrix, has been a major constraint to worldwide coffee production. Recently, H. vastatrix populations were shown to be structured into three divergent genetic lineages with marked host specialization (C1, C2, and C3). However, there is yet no overall understanding of the population dynamics and adaptation of the most widespread and epidemiological relevant H. vastatrix group (C3). We used restriction site-associated DNA sequencing to generate 13,804 single nucleotide polymorphisms (SNPs) across a worldwide collection of 99 H. vastatrix isolates. Phylogenetic analyses uncovered a well-supported structuring within C3, with three main subgroups (SGs; SGI, SGII, and SGIII), which seem to reflect the historical distribution, breeding, and exchange of coffee cultivars. SGI shows a ladder-like diversification pattern and occurs across all four continents sampled, SGII is mainly restricted to Africa, and SGIII is observed only in Timor, revealing a higher genetic differentiation. Outlier and association tests globally identified 112 SNPs under putative positive selection, which impacted population structure. In particular, 29 overlapping SNPs per se seemed to have an extremely strong effect on H. vastatrix population divergence. We also found exclusive and fixed alleles associated with the SGs supporting local adaptation. Functional annotation revealed that transposable elements may play a role in host adaptation. Our study provides a higher-resolution perspective on the evolutionary history of H. vastatrix on cultivated coffee, showing its strong ability to adapt and the strength of the selective force imposed by coffee hosts, which should be taken into account when designing strategies for pathogen dissemination control and selective breeding.
Immediate Breast Reconstruction in an 11-year-old Girl with a Large Malignant Phyllodes Tumor
Authors: Serhan Karolina A. , Kemp Tamara L.
Published: March 2022

Phyllodes tumors are rare fibroepithelial breast tumors representing less than 1% of all breast malignancies, with an extremely uncommon presence in the pediatric population.
1
Although prognosis is favorable following excision given their indolent course, they often grow rapidly and frequently recur. As such, they can present unique oncologic and reconstructive challenges. Herein we present a case of a malignant phyllodes tumor in an 11-year-old girl treated with total skin-sparing mastectomy and adjustable saline implant, and explore the reconstructive challenges of this unique case.
MULTIMODAL IMAGING OF BILATERAL IDIOPATHIC MULTIFOCAL RETINAL PIGMENT EPITHELIAL DETACHMENTS IN YOUNG PATIENTS
Authors: Alhumaid Sulaiman , Ashkenazy Noy , Hudson Julia L. , Berrocal Audina M. , Flynn Harry W.
Published: March 2022

Purpose:

The aim of this study was to describe two cases of multiple epithelial detachments (pigment epithelial detachments [PEDs]) occurring in otherwise young, healthy patients.

Methods:

The medical and imaging records of two cases were reviewed retrospectively.

Results:

Multiple serous nonvascularized PEDs were present in two young, healthy patients who underwent multimodal imaging. The first patient, a 38-year-old woman, was incidentally found to have a visual acuity of 20/20 in both eyes and multiple bilateral PEDs. Imaging and a systemic work-up was negative for secondary causes, and at 36 months, vision remained stable although some of the PEDs had coalesced. The second patient, a 32-year-old woman, presented with distortion and perceived scotomas in both eyes progressive over the course of 2 years. The visual acuity was 20/20, and multimodal imaging confirmed the presence of bilateral PEDs.

Conclusion:

Bilateral idiopathic multifocal retinal PEDs in otherwise healthy young adults is a rare condition. Longer term follow-up is needed to evaluate secondary complications and visual outcomes.
Rapid Office-Based Diagnosis of Demodex Using an Innovative Smartphone-Aided Intraocular Lens Tool
Authors: Gosalia Hirika , Chandrakanth Prithvi , Verghese Shishir , Rammohan Ram , Narendran Kalpana , Narendran Venkatapathy
Published: March 2022

Demodex is an important pathogen causing eyelid and eyelash diseases. This article describes a quick, efficient, cost-effective office-based imaging of demodex with the help of an intraocular lens (IOL) and smartphone-aided innovated tool. Eyelid photography of a 56-year-old man with suspected demodex infestation was obtained using a 20-diopter (D) IOL over the smartphone camera called as Anterior Segment Photography using IOL (ASPI). A video or photograph of the epilated eyelash was taken using four 30-D IOLs attached to the smartphone camera to form an optical system called IOLSCOPE, which clearly detected the demodex parasite. The importance of ASPI and IOLSCOPE for the rapid office-based diagnosis of demodex pathogen in peripheral health centers devoid of slitlamp and microscopes has been emphasized here.
Experiences of Treatment With Contact Lenses in Aphakic Children With Unilateral Congenital Cataract: A Retrospective Study
Authors: Kooshki Abdolreza M. , Kooshki Ashkan M. , Yaseri Mehdi , Nouri Leila , Alipour Fateme
Published: March 2022

Background and Objectives:

Congenital cataract is a condition compromising the eye's crystalline lens in infants and is usually diagnosed at birth. It can lead to irreversible vision loss if not promptly detected and treated, especially in unilateral cases. Nowadays, children with congenital cataracts can undergo surgical removal of their opacified crystalline lenses, and visual rehabilitation is mandatory to prevent deep amblyopia. Contact lenses, predominantly of rigid gas-permeable (GP) type, are gaining more popularity for this matter.

Method:

In this retrospective cohort study, unilateral aphakic children younger than 6 years referred to the Contact Lens Clinic at Farabi Eye Hospital from November 2011 to September 2019 were included.

Results:

Seventy-six unilateral aphakic children with congenital cataracts (57.9% boys and 42.1% girls) rehabilitated with GP were studied. The mean age of diagnosis and referral to the contact lens clinic were 20.0±19.8 and 32.0±24.4 weeks, respectively, while the mean follow-up time was 12.44±26.28 months. The mean visual acuity for children capable of cooperating at the last follow-up was 0.98±0.62 log MAR. Among the participants, eight children (9.7%) were diagnosed as glaucoma suspects. The mean initial base curve and power of GP lenses were 7.86±0.39 mm and 23.29±5.52 diopters, respectively. Only 21 parents (27.6%) reported nonadherence to the scheduled part-time patch program.

Conclusion:

The results of this study showed GP-based optical treatment after early diagnosis, surgical removal of congenital cataracts, and a long-term close follow-up to be well tolerated by children and their parents, with acceptable parents' compliance and can thus be introduced as a safe and effective method to achieve desirable visual outcomes.
Temporal and Spatial Assessment of the Corneal Response to UV Cross-Linking Using 3-Dimensional In Vivo Confocal Microscopy
Authors: Parsa Shyon , Rodriguez Alejandro , Robertson Danielle M. , Bowman Robert Wayne , Petroll Walter Matthew
Published: March 2022

The goal of this study was to evaluate the temporal and spatial pattern of wound healing following UV corneal cross-linking (CXL) using 3-dimensional (3-D) confocal imaging in vivo. Using a modified Heidelberg Retinal Tomograph with Rostock Corneal Module confocal microscope, we performed 3-D scans on two patients at multiple time points after CXL. Patient 1 showed a normal post-CXL wound healing response, with initial subbasal nerve loss and keratocyte apoptosis in the anterior stroma, followed by partial restoration of both the nerve plexus and stromal keratocytes by 6 months. In patient 2, in addition to anterior corneal damage, pyknotic nuclei were observed in the posterior stroma 7 days after CXL. Acellular areas were present in the posterior stroma at 3 months, with only partial keratocyte repopulation at 6 months. Regeneration of the subbasal nerve plexus was also delayed. Three-dimensional confocal imaging allowed these unusual wound healing responses to be identified in the absence of any corresponding clinical observations.
Characteristics of Higher-Order Aberrations in Different Stages of Keratoconus
Authors: Koh Shizuka , Inoue Ryota , Maeno Sayo , Mihashi Toshifumi , Maeda Naoyuki , Jhanji Vishal , Nishida Kohji
Published: March 2022

Objectives:

To characterize higher-order aberrations (HOAs) in clinical and subclinical keratoconus (KC).

Methods:

The study included 33, 36, and 26 patients with clinical, topographic (no clinical signs), and pretopographic (normal topography and no clinical signs) KC and 30 controls. Ocular and corneal HOAs for the 4-mm pupils were measured using a wavefront sensor and expanded up to the sixth order of Zernike polynomials. The magnitudes of trefoil, coma, tetrafoil, secondary astigmatism, and spherical aberration were calculated via Zernike vector analysis and used as HOA parameters along with total HOAs. Area under the receiver operating characteristic curve (AUROC) values for each wavefront parameter for pretopographic KC were compared.

Results:

Control eyes and eyes with pretopographic KC had significantly lower ocular or corneal total HOAs and Zernike vector terms than those with clinical KC and topographic KC, except for ocular tetrafoil between topographic KC and pretopographic KC and spherical aberration among all groups. The AUROCs for corneal total HOAs and corneal coma for pretopographic KC and control eyes were 0.781 (100% sensitivity and 47% specificity) and 0.735 (73% sensitivity and 73% specificity), respectively.

Conclusion:

Corneal total HOAs and corneal coma exhibited a potential ability to discriminate pretopographic KC from normal control eyes.
Association between chronic low back pain and regional brain atrophy in a Japanese older population: the Hisayama Study
Authors: Asada Masako , Shibata Mao , Hirabayashi Naoki , Ohara Tomoyuki , Furuta Yoshihiko , Nakazawa Taro , Honda Takanori , Hata Jun , Hosoi Masako , Sudo Nobuyuki , Yamaura Ken , Ninomiya Toshiharu
Published: March 2022

Chronic low back pain (CLBP) is the leading cause of years lived with disability. Recently, it has been reported that CLBP is associated with alterations in the central nervous system. The present study aimed to investigate the association between CLBP and regional brain atrophy in an older Japanese population. A total of 1106 community-dwelling participants aged ≥65 years underwent brain magnetic resonance imaging scans and a health examination in 2017 to 2018. We used the FreeSurfer software for the analysis of brain magnetic resonance imaging. Chronic pain was defined as subjective pain for ≥3 months. Participants were divided into 3 groups according to the presence or absence of chronic pain and the body part that mainly suffered from pain: a “no chronic pain (NCP)” group (n = 541), “CLBP” group (n = 189), and “chronic pain in body parts other than the lower back (OCP)” group (n = 376). The brain volumes of the ventrolateral and dorsolateral prefrontal cortex, the posterior cingulate gyrus, and the amygdala were significantly lower in the CLBP group than in the NCP group after adjustment for sociodemographic, physical, and lifestyle factors and depressive symptoms. In addition, the left superior frontal gyrus was identified as a significant cluster by the Query, Design, Estimate, Contrast interface. There were no significant differences in the brain volumes of pain-related regions between the NCP and the OCP groups. The present study suggests that CLBP is associated with lower brain volumes of pain-related regions in a general older population of Japanese.
Patterns of Enrollment in Cancer Treatment Trials During the COVID-19 Pandemic at National Cancer Institute–Designated Cancer Centers
Authors: Prindiville Sheila A. , Sarosy Gisele A. , Loose David , Ciolino Henry , Doroshow James H.
Published: March 2022

The COVID-19 pandemic posed unprecedented strain on enrollment to cancer clinical trials and their conduct. Here, we highlight an analysis using information from the National Cancer Institute (NCI) Clinical Trials Reporting Program database to describe enrollment patterns to interventional cancer treatment trials at NCI-Designated Cancer Centers during the pandemic. Enrollment to cancer treatment trials at NCI-Designated Cancer Centers decreased precipitously early in the pandemic and has not yet fully returned to the 2019 baseline as of mid-2021. We discuss possible reasons for this and how some of the changes in clinical trial conduct implemented during the pandemic may become part of the standard conduct of NCI-supported clinical trials and broaden access to trials.
Lessons From the Impact of the COVID-19 Pandemic at the National Cancer Institute
Authors: Karzai Fatima , Dahut William L.
Published: March 2022

The COVID-19 (coronavirus disease 2019) pandemic has worldwide implications on health care, especially in our most vulnerable population: cancer patients. Flexibility and adaptation are needed to continue clinical research and for clinical trial development. At the Intramural Research Program, National Cancer Institute, swift changes have been implemented to protect our patients while maintaining the scientific integrity of our cancer clinical trials. Many lessons have been learned including incorporation of telehealth into clinical trials, partnerships with the oncology community at both academic institutions and community practices, focusing on diversity and inclusion to improve scientific innovation, and strengthened relationships with regulatory agencies and institutional review boards. These changes will enhance the clinical trials we conduct well beyond the pandemic.
Clinical Evidence Generation During a Pandemic
Authors: Rivera Donna R. , Kluetz Paul G. , Abdallah Kald , Agrawal Sundeep , Angus Derek C. , Califf Robert M. , Garrett-Mayer Elizabeth , Hyer Randall , Lowy Douglas R. , Khleif Samir N.
Published: March 2022

Because of significant adaptations forced by the COVID-19 pandemic, resultant changes within health care delivery and clinical research introduced the potential for evaluation of novel evidence generation approaches in oncology. On July 26 and 27, 2021, the National Academies of Science, Engineering, and Medicine, National Cancer Policy Forum hosted a virtual workshop entitled “Cancer Care and Cancer Research in the Context of the COVID-19 Pandemic: A Workshop on Lessons Learned.” This workshop examined changes in cancer care and cancer research that occurred in response to the COVID-19 pandemic and considered lessons learned from that experience. The goal was to identify what changes could improve the delivery of high-quality cancer care and the conduct of cancer clinical trials in the postpandemic era, with an emphasis on health equity. How can we sustain the valuable lessons learned that might accelerate progress and enhance clinical evidence generation for patients and clinicians? In this overview, we discuss ways in which the COVID-19 experience has catalyzed research efficiencies as well as fostered a broader array of trial design and research methods that may facilitate improved cancer drug development during the pandemic and beyond.
Outcomes after application of halothoracic orthosis for cervical spine trauma
Authors: Steiner Joel , Kimmel Lara A. , Tomkins Jonathan B. , Wheeler Karly N. , Liew Susan
Published: March 2022

Background:

Cervical spine fractures can be managed operatively or nonoperatively, considering injury type and patient factors. Nonoperative management may include application of a halothoracic orthosis (HTO). The aim of our study was to describe our patients managed with HTO, review their 6-month and 12-month outcomes, and identify associated factors.

Methods:

Patients fitted with an HTO at our institution in 2014 were included. Data collected included patient demographics, hospital-related data, and radiological union. Injury detail and 6-month and 12-month patient-reported outcomes (Glasgow Outcomes Scale Extended and return to work [RTW]) were accessed through Victorian Orthopedic Trauma Outcomes Registry. Factors related to these outcomes were included in a mixed-effect regression model for each outcome.

Results:

Eighty-six patients (median age 46.5 years) of whom 52 (60%) were male individuals were included. Two-thirds (57 patients) were road trauma patients, and 58 patients (67%) experienced an isolated injury. Thirty-seven patients (43%) experienced a C2 fracture and 27 (31%) experienced a facet fracture. Twelve-month follow-up was completed for 78 patients (91%) with 27 (35%) reporting a good recovery, and 65% (31/48) patients returned to work. Factors associated with lower odds of RTW included compensation, a facet joint fracture, and experiencing comorbidities. No factors were significantly associated with functional outcome, although female individuals exhibited a slower recovery trajectory than male individuals.

Conclusion:

Many patients reported poor 12-month outcomes after HTO for traumatic injury. Factors associated with worse outcomes should be considered when deciding on management of patients with cervical spine fractures.
Correlation between kinesthetic motor imagery of an amputated limb and phantom limb pain
Authors: Yoshimura Manabu , Kurumadani Hiroshi , Hirata Junya , Date Shota , Ueda Akio , Ishii Yosuke , Senoo Katsutoshi , Hanayama Kozo , Sunagawa Toru
Published: March 2022

Background:

Phantom limb pain (PLP) is a frequent painful sensation in amputees, and motor imagery (MI) is a useful approach for the treatment of this type of pain. However, it is not clear regarding the best MI modality for PLP.

Objectives:

The purpose of this study was to investigate the relationship between the PLP and MI modality in upper limb amputees.

Study design:

Observational study.

Methods:

Eleven patients who underwent unilateral upper limb amputation participated in this study. The MI modality (kinesthetic and visual) and PLP intensity were evaluated using the Kinesthetic and Visual Imagery Questionnaire (KVIQ)-20 and a visual analog scale. MI ability was also assessed during the hand mental rotation task. We examined the correlation between MI modalities, ability, and pain intensity.

Results:

The total KVIQ kinesthetic score was negatively correlated with pain intensity (r = −0.71, P < 0.01): the more vivid the kinesthetic imagery, the weaker the pain. In particular, the reduction in pain intensity was associated with strong kinesthetic imagery of opposing movements of the deficient thumb (r = −0.81, P < 0.01). The KVIQ visual score and MI ability were not associated with pain intensity.

Conclusions:

Our data showed that the reduction of PLP could be associated with the kinesthetic modality of MI but not with visual modality or MI ability. In other words, it was suggested that the more vivid the sensation of moving muscles and joints in the defect area, the lower the PLP intensity. To reduce PLP, clinicians may prefer interventions using the kinesthetic modality.
Polypharmacy Is Associated With Falls in Women With and Without HIV
Authors: Psomas Christina K. , Hoover Donald R. , Shi Qiuhu , Brown Todd T. , Vance David E. , Holman Susan , Plankey Michael W. , Tien Phyllis C. , Weber Kathleen M. , Floris-Moore Michelle , Bolivar Hector H. , Golub Elizabeth T. , McDonnell Holstad Marcia , Radtke Kendra K. , Tamraz Bani , Erlandson Kristine M. , Rubin Leah H. , Sharma Anjali
Published: March 2022

Background:

Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between polypharmacy (use of 5 or more non-ART medications), use of neurocognitive adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV−).

Methods:

Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH and 557 HIV-) Women's Interagency HIV Study participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk.

Results:

The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51% vs. 41%; P < 0.001) and NCAE medication use (44% vs. 37%; P = 0.01) than HIV- women. Polypharmacy conferred elevated odds of single fall [adjusted odds ratio (aOR) 1.67, 95% CI: 1.36 to 2.06; P < 0.001] and multiple falls (aOR 2.31, 95% CI: 1.83 to 2.93; P < 0.001); the results for NCAE medications and falls were similar. Both polypharmacy and number of NCAE medications remained strongly and independently associated with falls in multivariable models adjusted for HIV serostatus, study site, sociodemographics, clinical characteristics, and substance use.

Conclusions:

Polypharmacy and NCAE medication use were greater among WWH compared with HIV-, and both were independently and incrementally related to falls. Deprescribing and avoidance of medications with NCAEs may be an important consideration for reducing fall risk among WWH and sociodemographically similar women without HIV.
Thiosulfatihalobacter marinus gen. nov. sp. nov., a novel member of the family Roseobacteraceae, isolated from the West Pacific Ocean
Authors: Wu Yuehong , Ren Wen-Ting , Zhong Ying-Wen , Guo Li-Li , Zhou Peng , Xu Xue-Wei
Published: March 2022

Two strains (GL-11-2T and ZH2-Y79) were isolated from the seawater collected from the West Pacific Ocean and the East China Sea, respectively. Cells were Gram-stain-negative, strictly aerobic, non-motile and rod-shaped. Cells grew in the medium containing 0.5–7.5 % NaCl (w/v, optimum, 1.0–3.0 %), at pH 6.0–8.0 (optimum, pH 6.5–7.0) and at 4–40 °C (optimum, 30 °C). H2S production occurred in marine broth supplemented with sodium thiosulphate. The almost-complete 16S rRNA gene sequences of the two isolates were identical, and exhibited the highest similarity to

Pseudoruegeria aquimaris

JCM 13603T (97.5 %), followed by

Ruegeria conchae

TW15T (97.2%),

Shimia aestuarii

DSM 15283T (97.1 %) and

Ruegeria lacuscaerulensis

ITI-1157T (97.0 %). Phylogenetic analysis revealed that the isolates were affiliated with the family

Roseobacteraceae

and represented an independent lineage. The sole isoprenoid quinone was ubiquinone 10. The principal fatty acids were summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c) and cyclo-C19 : 0
 ω8c. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and diphosphatidylglycerol. The DNA G+C content was 62.3 mol%. The orthologous average nucleotide identity, in silico DNA–DNA hybridization and average amino acid identity values among the genomes of strain GL-11-2T and the reference strains were 73.2–79.0, 20.3–22.5 and 66.0–80.8 %, respectively. Strains GL-11-2ᵀ and ZH2-Y79 possessed complete metabolic pathways for thiosulphate oxidation, dissimilatory nitrate reduction and denitrification. Phylogenetic distinctiveness, chemotaxonomic differences and phenotypic properties revealed that the isolates represent a novel genus and species of the family

Roseobacteraceae

, belonging to the class

Alphaproteobacteria

, for which the name Thiosulfatihalobacter marinus gen. nov., sp. nov. (type strain, GL-11–2T=KCTC 82723T=MCCC M20691T) is proposed.
Intra-macrophage expression of ArtAB toxin gene in Salmonella
Authors: Miura Shou , Satoh Rin , Tamamura-Andoh Yukino , Tokugawa Kanetaka , Beppu Miho , Nozaki Chiharu , Murata Ryo , Kusumoto Masahiro , Uchida Ikuo
Published: March 2022

Salmonella entericasubspeciesentericaserovar Typhimurium (S. Typhimurium) definitive phage type 104 (DT104),S. Worthington, andS. bongoriproduce ArtAB toxin, which catalyses ADP-ribosylation of pertussis toxin-sensitive G protein. ArtAB gene (artAB) is encoded on a prophage inSalmonella, and prophage induction by SOS-inducing agents is associated with increases in ArtAB productionin vitro. However, little is known about the expression ofartAB in vivo. Here, we showed a significant increase inartABtranscription of DT104 within macrophage-like RAW264.7 cells. Intracellular expression of ArtAB was also observed by immunofluorescence staining. The induced expression ofartABin DT104 andS. bongoriwas enhanced by treatment of RAW264.7 cells with phorbol 12-myristate 13-acetate (PMA), which stimulates the production of reactive oxygen species (ROS); however, such induction was not observed inS. Worthington. Upregulation ofoxyR, a major regulator of oxidative stress, andcI,a repressor of prophage induction, was observed inS. Worthington within RAW264.7 cells treated with PMA but not in the DT104 strain. Although the expression ofoxyRwas increased,artABwas upregulated inS. bongori,which lacks thecIgene in the incompleteartAB-encoded prophage. Taken together, oxidative stress plays a role in the production ofartABtoxins in macrophages, and high expression levels ofoxyRandcIare responsible for the low expression ofartAB. Therefore, strain variation in the level ofartABexpression within macrophages could be explained by differences in the oxidative stress response of bacteria and might be reflected in its virulence.
Exposure to the Pseudomonas aeruginosa secretome alters the proteome and secondary metabolite production of Aspergillus fumigatus
Authors: Margalit Anatte , Sheehan David , Carolan James C. , Kavanagh Kevin
Published: March 2022

The fungal pathogen Aspergillus fumigatus is frequently cultured from the sputum of cystic fibrosis (CF) patients along with the bacterium Pseudomonas aeruginosa. A. fumigatus secretes a range of secondary metabolites, and one of these, gliotoxin, has inhibitory effects on the host immune response. The effect of

P. aeruginosa

culture filtrate (CuF) on fungal growth and gliotoxin production was investigated. Exposure of A. fumigatus hyphae to

P. aeruginosa

cells induced increased production of gliotoxin and a decrease in fungal growth. In contrast, exposure of A. fumigatus hyphae to

P. aeruginosa

CuF led to increased growth and decreased gliotoxin production. Quantitative proteomic analysis was used to characterize the proteomic response of A. fumigatus upon exposure to

P. aeruginosa

CuF. Changes in the profile of proteins involved in secondary metabolite biosynthesis (e.g. gliotoxin, fumagillin, pseurotin A), and changes to the abundance of proteins involved in oxidative stress (e.g. formate dehydrogenase) and detoxification (e.g. thioredoxin reductase) were observed, indicating that the bacterial secretome had a profound effect on the fungal proteome. Alterations in the abundance of proteins involved in detoxification and oxidative stress highlight the ability of A. fumigatus to differentially regulate protein synthesis in response to environmental stresses imposed by competitors such as

P. aeruginosa

. Such responses may ultimately have serious detrimental effects on the host.
The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke
Authors: Sharif Massoud S. , Goldberg Emily B. , Walker Alexandra , Hillis Argye E. , Meier Erin L.
Published: March 2022

Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. Compared to subcortical stroke patients without aphasia, patients with aphasia had greater acute and total lesion volume, were older, and had significantly greater damage to the internal capsule (which did not survive controlling for total lesion volume). Patients with aphasia did not differ from non-aphasic patients by other demographic or stroke variables. Age was the only significant predictor of aphasia status in a logistic regression model. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.
Pin1-promoted SUMOylation of RNF168 restrains its chromatin accumulation
Authors: Chauhan Anoop Singh , Garvin Alexander J. , Jamshad Mohammed , Morris Joanna R.
Published: March 2022

The E3 ubiquitin ligase RNF168 is a rate-limiting component of DNA double-strand break signalling that acts to amplify histone ubiquitylation. The confining of RNF168 chromatin spreading around DNA break sites has been related to constraining its expression levels and to the removal of ubiquitin-conjugates to which it binds. Here we identify a new mechanism that suppresses RNF168 amplification at chromatin. We show that depletion of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) or mutation of the Pin1-binding site of RNF168 increases DNA-damage site accumulation of RNF168 to supraphysiological levels without impacting RNF168 expression levels. Pin1 promotes SUMOylation of RNF168 by SUMO2/3, and a SUMO conjugation site on RNF168 is required to restrict RNF168 accumulations. We find Pin1-SUMO mediated-regulation of RNF168 is associated with cellular radioresistance. These data demonstrate that the regulation of chromatin ubiquitylation is actively suppressed by modification of RNF168 to counteract excessive RNF168-ubiquitin spreading.
Hyperactive immature state and differential CXCR2 expression of neutrophils in severe COVID-19
Authors: Rice Christopher M. , Lewis Philip , Ponce-Garcia Fernando M. , Gibbs Willem , Cela Drinalda , Hamilton Fergus , Arnold David , Hyams Catherine , Oliver Elizabeth , Barr Rachael , Goenka Anu , Davidson Andrew , Wooldridge Linda , Finn Adam , Rivino Laura , Amulic Borko
Published: March 2022

Neutrophils are vital in defence against pathogens but excessive neutrophil activity can lead to tissue damage and promote acute respiratory distress syndrome (ARDS). COVID-19 is associated with systemic expansion of immature neutrophils but the functional consequences of this shift to immaturity are not understood. We used flow cytometry to investigate activity and phenotypic diversity of circulating neutrophils in acute and convalescent COVID-19 patients. First, we demonstrate hyperactivation of immature CD10−subpopulations in severe disease, with elevated markers of secondary granule release. Partially activated immature neutrophils were detectable three months post symptom onset, indication long term myeloid dysregulation in convalescent COVID-19 patients. Second, we demonstrate that neutrophils from moderately ill patients downregulate the chemokine receptor CXCR2, while neutrophils from severely ill individuals failed to do so, suggesting altered ability for organ trafficking and a potential mechanism for induction of disease tolerance. CD10−and CXCR2hineutrophil subpopulations were enriched in severe disease and may represent prognostic biomarkers for identification of individuals at high risk of progressing to severe COVID-19.
A weakly structured stem for human origins in Africa
Authors: Ragsdale Aaron P. , Weaver Timothy D. , Atkinson Elizabeth G. , Hoal Eileen , Möller Marlo , Henn Brenna M. , Gravel Simon
Published: March 2022

While it is now broadly accepted that Homo sapiens originated within Africa, considerable uncertainty surrounds specific models of divergence and migration across the continent. Progress is hampered by a paucity of fossil and genomic data, as well as variability in prior divergence time estimates. Here we use linkage disequilibrium and diversity-based statistics, optimized for rapid, complex demographic inference to discriminate among such models. We infer detailed demographic models for populations across Africa, including representatives from eastern and western groups, as well as 44 newly whole-genome sequenced individuals from the Nama (Khoe-San). Despite the complexity of African population history, contemporary population structure dates back to Marine Isotope Stage (MIS) 5. The earliest population divergence among contemporary populations occurs 120-135ka, between the Khoe-San and other groups. Prior to the divergence of contemporary African groups, we infer long-lasting structure between two or more weakly differentiated ancestral Homo populations connected by gene flow over hundreds of thousands of years (i.e. a weakly structured stem). We find that weakly structured stem models provide more likely explanations of polymorphism that had previously been attributed to contributions from archaic hominins in Africa. In contrast to models with archaic introgression, we predict that fossil remains from coexisting ancestral populations should be morphologically similar. Despite genetic similarity between these populations, an inferred 1–4% of genetic differentiation among contemporary human populations can be attributed to genetic drift between stem populations. We show that model misspecification explains variation in previous divergence time estimates and argue that studying a suite of models is key to robust inferences about deep history.
Structural insights into the viral proteins binding by TRIM7 reveal a general C-terminal glutamine recognition mechanism
Authors: Liang Xiao , Xiao Jun , Li Xuzichao , Wen Yanan , Che Xing , Ma Yongjian , Zhang Xingyan , Zhang Yi , Jian Deng , Wang Peihui , Xuan Chenghao , Yu Guimei , Li Long , Zhang Heng
Published: March 2022

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. A recent study found that TRIM7 inhibits human enteroviruses through ubiquitination and proteasomal degradation of viral 2BC protein by targeting the 2C moiety of 2BC protein. Here, we report the crystal structures of TRIM7 in complex with 2C, where the C-terminal region of 2C is inserted into a positively charged groove of the TRIM7 PRY-SPRY domain. Structure-guided biochemical studies revealed the C-terminus glutamine residue of 2C as the primary determinant for TRIM7 binding. Such a glutamine-end motif binding mechanism can be successfully extended to other substrates of TRIM7. More importantly, leveraged by this finding, we were able to identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. We further show that TRIM7 may function as a restriction factor to promote the degradation of the viral proteins of norovirus and SARS-CoV-2, thereby restoring the Type I interferon immune response and inhibiting viral infection. Several crystal structures of TRIM7 in complex with SARS-CoV-2 proteins are also determined, and a conserved C-terminus glutamine-specific interaction is observed. These findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.
Loss of transgene expression limits liver gene therapy in primates
Authors: Greig Jenny A. , Breton Camilo , Martins Kelly M. , Zhu Yanqing , He Zhenning , White John , Bell Peter , Wang Lili , Wilson James M.
Published: March 2022

Introductory Paragraph

Efforts to improve liver gene therapy have focused on next-generation adeno-associated virus (AAV) vector capsids, transgene delivery, and immunomodulating drugs, such as corticosteroids, to avoid destructive T-cell responses. We conducted a detailed characterization of AAV transduction in nonhuman primate liver across multiple capsids and transgenes to better define interactions that may limit stable and efficient transgene expression. We show that the initial transduction of hepatocytes is high, but the transduction rapidly diminishes to a lower stable baseline of <1% of cells, even though ~10% of the cells retain vector DNA that is localized within the nucleus. Further characterization showed genomic vector integration at frequencies of 1/100 to 1/1,000 genomes, suggesting that one mechanism for stable expression may occur via genome integration. These studies suggest that strategies to enhance durable transgene expression by activating retained nuclear episomes or by increasing the frequency of vector integrations may improve liver directed AAV gene therapy.
HRTex: a high-resolution texture data processing tool for monochromatic neutron diffraction based on the pixel projection method
Authors: Yang Jian , Zhong Shengyi , Luzin Vladimir , Li Jian , Liu Xiaolong , Dan Chengyi
Published: March 2022

HRTex is a new texture data processing tool for two-dimensional position-sensitive area detectors on monochromatic neutron diffractometers. With the aim of improving the resolution and accuracy of pole figure calculations, HRTex treats the raw data of the area detector for each pixel and projects the intensity of each pixel directly onto a high-resolution pole figure. With the resultant refinement of the resolution, HRTex can distinguish close texture peaks with a flexible resolution setting and reduced information loss. Test results of HRTex on the data sets of two samples measured by two different neutron facilities are analysed, and the improvements in accuracy, resolution and efficiency of the pole figure calculation are discussed.
A collaborative trend prediction method using the crowdsourced wisdom of web search engines
Authors: Fang Ze-Han , Chen Chien Chin
Published: March 2022

Purpose

The purpose of this paper is to propose a novel collaborative trend prediction method to estimate the status of trending topics by crowdsourcing the wisdom in web search engines. Government officials and decision makers can take advantage of the proposed method to effectively analyze various trending topics and make appropriate decisions in response to fast-changing national and international situations or popular opinions.

Design/methodology/approach

In this study, a crowdsourced-wisdom-based feature selection method was designed to select representative indicators showing trending topics and concerns of the general public. The authors also designed a novel prediction method to estimate the trending topic statuses by crowdsourcing public opinion in web search engines.

Findings

The authors’ proposed method achieved better results than traditional trend prediction methods and successfully predict trending topic statuses by using the crowdsourced wisdom of web search engines.

Originality/value

This paper proposes a novel collaborative trend prediction method and applied it to various trending topics. The experimental results show that the authors’ method can successfully estimate the trending topic statuses and outperform other baseline methods. To the best of the authors’ knowledge, this is the first such attempt to predict trending topic statuses by using the crowdsourced wisdom of web search engines.