bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the effect of oil inlet size on the static performance characteristics of non-Newtonian lubricated hole-entry hybrid journal bearings
Authors: Cao Haiyin , Huang Yu , Rong Youmin , Wu Hao , Guo Minghui
Published: August 2021

In this study, the influence of inlet pocket size on the static performance of non-Newtonian lubricated hole-entry hybrid journal bearings is theoretically analyzed. The oil film of the bearing is discretized into a nonuniform mesh containing the geometric characteristics of the oil inlet pocket, and the inlet pocket is treated as a micro-oil recess. The Reynolds equation is solved by the finite element method based on Galerkin's techniques, and a new solution strategy to solve the recess/pocket pressure is proposed. The power-law model is used to introduce the non-Newtonian effect. The results show that the static performance characteristics of this type of bearing are greatly affected by the pocket size at both zero speed and high speed.
Successful laparoscopic removal of ovarian borderline cystadenoma in patient with multiorgan hemangioma and ventriculoperitoneal shunt: a case report and literature review
Authors: Zhang Chenyi , Jing Xinhui
Published: August 2021

As medical diagnosis and treatment level improved, patients with ventriculoperitoneal shunt (VPS) live longer and may develop conditions that need laparoscopic surgery. The safety of laparoscopy in patients with VPS continues to be challenged due to pneumoperitoneum. Here, we report a patient with medical history of VPS and hemangioma, diagnosed with ovarian borderline mucinous cystadenoma, received laparoscopic surgery in supine position and 10 mmHg pneumoperitoneum pressure, in which no clamping or externalizing catheter, no perioperative or postoperative complications. We also present a literature review and discuss the precautions needing considering during laparoscopy. For patients with VPS, laparoscopic surgery can be recognized as a potentially safe and feasible procedure.
Jewish Orthodoxy’s First Rabbinical Conference
Authors: Keren-Kratz Menachem
Published: August 2021

The early stages in the formation of the movement that would subsequently become known as Jewish Orthodoxy have been well researched. This article, however, reviews the circumstances around a specific episode, a rabbinical conference held in Paks, Hungary, in 1844. The review of this failed conference opens the door for a discussion on three key questions related to the understanding of Jewish Orthodoxy: (a) Why were the Hungarian rabbis the first to react to religious reforms? (b) Why did they become so instrumental in the establishment of Jewish Orthodoxy? and (c) Why, despite this, Orthodoxy practically lost the war against modernism, religious reforms, and secularism.

Analyzing the reasons for the conference’s failure suggests that Jewish Orthodoxy, which is committed to a traditionalist worldview, contains a major intrinsic flaw. Hailing conservatism also implies rejecting initiatives based on modern modes of operation. This, however, undermined Jewish Orthodoxy’s capability to swiftly and decisively confront the numerous social and religious challenges it has faced since the early nineteenth century. The Paks conference was convened in response to several conferences of modernized rabbis that led to the establishment of the Reform Movement; its failure allowed the Reform movement to expand without any significant resistance on behalf of the more conservative rabbis, who remained unorganized for many years.
Peculiar velocities in the local Universe: comparison of different models and the implications for H0 and dark matter
Authors: Boruah Supranta S , Hudson Michael J , Lavaux Guilhem
Published: August 2021

When measuring the value of the Hubble parameter, H0, it is necessary to know the recession velocity free of the effects of peculiar velocities. In this work, we study different models of peculiar velocity in the local Universe. In particular, we compare models based on density reconstruction from galaxy redshift surveys and kernel smoothing of peculiar velocity data. The velocity field from the density reconstruction is obtained using the 2M++ galaxy redshift compilation, which is compared to two adaptive kernel-smoothed velocity fields: the first obtained from the 6dF Fundamental Plane sample and the other using a Tully–Fisher catalogue obtained by combining SFI++ and 2MTF. We highlight that smoothed velocity fields should be rescaled to obtain unbiased velocity estimates. Comparing the predictions of these models to the observations from a few test sets of peculiar velocity data, obtained from the Second Amendment Supernovae catalogue and the Tully–Fisher catalogues, we find that 2M++ reconstruction provides a better model of the peculiar velocity in the local Universe than the kernel-smoothed peculiar velocity models. We study the impact of peculiar velocities on the measurement of H0 from gravitational waves and megamasers. In doing so, we introduce a probabilistic framework to marginalize over the peculiar velocity corrections along the line of sight. For the megamasers, we find H0 = 70.1 ± 2.9 km s−1 Mpc−1 using the 2M++ velocity field. We also study the peculiar velocity of the galaxy NGC 1052-DF2, concluding that a short ∼13 Mpc distance is not a likely explanation of the anomalously low dark matter fraction of that galaxy.
Sequence specific integration by the family 1 casposase from CandidatusNitrosopumilus koreensis AR1
Authors: Wang Xiaoke , Yuan Qinling , Zhang Wenxuan , Ji Suyu , Lv Yang , Ren Kejing , Lu Meiling , Xiao Yibei
Published: August 2021

Casposase, a homolog of Cas1 integrase, is encoded by a superfamily of mobile genetic elements known as casposons. While family 2 casposase has been well documented in both function and structure, little is known about the other three casposase families. Here, we studied the family 1 casposase lacking the helix-turn-helix (HTH) domain from Candidatus Nitrosopumilus koreensis AR1 (Ca. N. koreensis). The determinants for integration by Ca. N. koreensis casposase were extensively investigated, and it was found that a 13-bp target site duplication (TSD) sequence, a minimal 3-bp leader and three different nucleotides of the TSD sequences are indispensable for target specific integration. Significantly, the casposase can site-specifically integrate a broad range of terminal inverted repeat (TIR)-derived oligonucleotides ranging from 7-nt to ∼4000-bp, and various oligonucleotides lacking the 5′-TTCTA-3′ motif at the 3′ end of TIR sequence can be integrated efficiently. Furthermore, similar to some Cas1 homologs, the casposase utilizes a 5′-ATAA-3′ motif in the TSD as a molecular ruler to dictate nucleophilic attack at 9-bp downstream of the end of the ruler during the spacer-side integration. By characterizing the family 1 Ca. N. koreensis casposase, we have extended our understanding on mechanistic similarities and evolutionary connections between casposons and the adaptation elements of CRISPR-Cas immunity.
Low tumor cell content predicts favorable prognosis in germinoma patients
Authors: Takami Hirokazu , Satomi Kaishi , Fukuoka Kohei , Fukushima Shintaro , Matsushita Yuko , Yamasaki Kai , Nakamura Taishi , Tanaka Shota , Mukasa Akitake , Saito Nobuhito , Suzuki Tomonari , Yanagisawa Takaaki , Nakamura Hideo , Sugiyama Kazuhiko , Tamura Kaoru , Maehara Taketoshi , Nakada Mitsutoshi , Nonaka Masahiro , Asai Akio , Yokogami Kiyotaka , Takeshima Hideo , Iuchi Toshihiko , Kanemura Yonehiro , Kobayashi Keiichi , Nagane Motoo , Kurozumi Kazuhiko , Yoshimoto Koji , Matsuda Masahide , Matsumura Akira , Hirose Yuichi , Tokuyama Tsutomu , Kumabe Toshihiro , Narita Yoshitaka , Shibui Soichiro , Nakazato Yoichi , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi
Published: August 2021

Background

Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response.

Methods

A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS).

Results

The tumor cell content was widely distributed from <5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (P = .002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (P = .03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (<50%) (P = .03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (P = .04). Among the 7 cases treated with local radiation and chemotherapy, all 3 cases that recurred (2 outside of the radiation field, 1 unknown) had tumor cell content of ≥50% in the original specimen, whereas all 4 cases without recurrence had tumor cell contents of <50%.

Conclusions

We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.
Post-ingestion conversion of dietary indoles into anticancer agents
Authors: Lin Li Ping , Liu Dan , Qian Jia Cheng , Wu Liang , Zhao Quan , Tan Ren Xiang
Published: August 2021

There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1) and 3,3′-diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM produced from I3C via the formaldehyde-releasing (major) and CO2-liberating (minor) pathways. In the large intestine, ‘endogenous’ I3C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H+-promotable steps. This work updates our understanding of the merits of I3C consumption and identifies LTr1 as a drug candidate.
Divergence equations and uniqueness theorem of static spacetimes with conformal scalar hair
Authors: Shinohara Takeshi , Tomikawa Yoshimune , Izumi Keisuke , Shiromizu Tetsuya
Published: August 2021

We reexamine the Israel-type proof of the uniqueness theorem of the static spacetime outside the photon surface in the Einstein-conformal scalar system. We derive in a systematic fashion a new divergence identity which plays a key role in the proof. Our divergence identity includes three parameters, allowing us to give a new proof of the uniqueness.
Integrin αvβ3-targeted polydopamine-coated gold nanostars for photothermal ablation therapy of hepatocellular carcinoma
Authors: Li Yang , Hu Ping , Wang Xiali , Hou Xu , Liu Fengzhen , Jiang Xiaohong
Published: August 2021

Photothermal therapy (PTT) has emerged as a promising cancer therapeutic method. In this study, Arg-Gly-Asp (RGD) peptide-conjugated polydopamine-coated gold nanostars (Au@PDA-RGD NPs) were prepared for targeting PTT of hepatocellular carcinoma (HCC). A polydopamine (PDA) shell was coated on the surface of gold nanostars by the oxidative self-polymerization of dopamine (termed as Au@PDA NPs). Au@PDA NPs were further functionalized with polyethylene glycol and RGD peptide to improve biocompatibility as well as selectivity toward the HCC cells. Au@PDA-RGD NPs showed an intense absorption at 822 nm, which makes them suitable for near-infrared-excited PTT. Our results indicated that the Au@PDA-RGD NPs were effective for the PTT therapy of the αVβ3 integrin receptor-overexpressed HepG2 cells in vitro. Further antitumor mechanism studies showed that the Au@PDA-RGD NPs-based PTT induced human liver cancer cells death via the mitochondrial–lysosomal and autophagy pathways. In vivo experiments showed that Au@PDA-RGD NPs had excellent tumor treatment efficiency and negligible side effects. Thus, our study showed that Au@PDA-RGD NPs could offer an excellent nanoplatform for PTT of HCC.
Fumigating Citrus with Phosphine Does Not Impact Marketability or Eating Quality
Authors: Obenland David , Cranney James R. , Tebbets Steve , Walse Spencer , Arpaia Mary Lu
Published: August 2021

To ensure control of arthropod pests, fresh citrus exports from the United States may be subject to postharvest phytosanitary treatment. Treatments, however, can potentially cause a phytotoxic response and damage the fruit. The main purpose of this study was to confirm that phosphine fumigation does not impact either the marketability or eating quality of citrus. Methyl bromide (MB) fumigation and cold treatment (CT) were included in the testing as comparisons. Treatments were conducted as if they were associated with an oceanic voyage of 28 days followed by 1 week at 10°C and then 1 week at 20°C to typify distribution and marketing conditions. Key quality parameters were evaluated, relative to nontreated controls, for each of three “predeparture” phosphine fumigations, an “on arrival” MB fumigation, and a 28-day CT at 1°C. The three phosphine treatments evaluated were 1.5 mg/liter for 12 h or 48 h at 5°C or for 48 h at 12°C. MB was applied at 64 mg/liter for 2 h at 5°C. In the second year, navel oranges were further evaluated using a sequential treatment in which a “predeparture” phosphine fumigation was followed by the “on arrival” MB fumigation. This work is the first to present results comparing phytosanitary treatments over multiple kinds of citrus and indicated that the phosphine treatments did not alter marketability or sensory quality for any of the citrus types. This contrasted with MB fumigation, which was damaging to the peel of all citrus, except Valencia oranges, and harmed grapefruit and mandarin flavor.
Psychosocial impact of ocular surface allergic inflammatory disorders
Authors: Mendelson Sivanne , Quintanilla Jaime , Norris Matthew R. , Bielory Leonard
Published: August 2021

Purpose of review

Allergic rhinoconjunctivitis is one of the most common ocular surface allergic inflammatory conditions seen in primary care that impacts patient's quality of life. Allergic conjunctivitis is increasingly being recognized as its own symptom complex that negatively impacts patient's quality of life separate from allergic rhinitis. This article reviews the psychosocial impact of ocular surface allergic inflammatory disorders (namely seasonal allergic conjunctivitis, ocular allergy, perennial allergic conjunctivitis, and atopic keratoconjunctivitis) on adult and pediatric populations.

Recent findings

Despite the perception that allergic conjunctivitis is a trivial condition, it imposes a burden on numerous psychosocial aspects of life for adolescents and adults. Several questionnaires specific to rhinoconjunctivitis have been found to be effective tools at gauging quality of life (QoL) and communicating impairments in specific behavioral domains for adult and pediatric populations. An emerging focus on the role of hormone fluctuations and age on ocular surface allergic inflammation underscores the importance of nuancing the physiologic effects on ocular allergy and QoL at every decade of life.

Further exploration and research of symptoms by age would greatly improve our understanding of age's impact on QoL in these patients and contribute to improved management of allergic conjunctivitis.
The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer
Authors: van Barele Mark , Buis Chistien C.M. , Brood-van Zanten Monique M.A. , van Doorn H. (Lena) C. , Gaarenstroom Katja N. , Heemskerk-Gerritsen Bernadette A.M. , Hooning Maartje J. , de Hullu Joanne , Mourits Marian J. , Burger Curt W.
Published: August 2021

Objective:

To compare the effect of tibolone to conjugated estrogens with medroxyprogesterone-acetate (CEE + MPA) on breast density, as a predictor for breast cancer risk, in women with a high risk of breast and ovarian cancer.

Methods:

Women aged 30-50 (N = 114) who had undergone risk-reducing salpingo-oophorectomy (RRSO) were randomized to tibolone or CEE + MPA.

Results:

Breast density decreased 46% after RRSO in untreated women, 39% after treatment with tibolone, and 17% after treatment with CEE + MPA; the decrease in breast density after CEE + MPA was significantly different compared with that of untreated women (P = 0.017).

Conclusions:

A decline in breast density is seen after premenopausal RRSO despite the use of both CEE + MPA or tibolone, although lower breast density is seen after tibolone use.
Autoantibodies in Patients With Immune-Related Adverse Events From Checkpoint Inhibitors
Authors: Ghosh Nilasha , Chan Karmela K. , Jivanelli Bridget , Bass Anne R.
Published: August 2021

Background

Immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) are sometimes associated with autoantibodies, but we do not know how frequently or whether these autoantibodies are present before ICI initiation. Our aim was to determine the positivity rate of autoantibodies in patients with organ-specific ICI-associated irAEs and determine their value as pretreatment biomarkers.

Methods

We searched for all English, peer-reviewed publications from MEDLINE, Embase, and Cochrane Library through February 20, 2020, and included any publication describing patients with irAEs and reporting results of any autoantibody investigation. Three reviewers independently extracted data, and 1 reviewer verified all data for accuracy and quality of reporting.

Results

We identified 515 publications. Most reports described endocrine, rheumatic, gastrointestinal/hepatic, and myositis/myasthenia/myocarditis irAEs. Autoantibodies were present in close to 50% of patients with ICI-associated endocrinopathies. Anti-BP180 was found in more than 50% of patients with skin irAEs. Antibodies were also common in patients with the triad of myositis/myasthenia/myocarditis including striational antibodies (49%), acetylcholine receptor antibodies (40%), and myositis-associated antibodies (27%). Only 11% of patients with arthritis had either rheumatoid factor or cyclic citrullinated peptide antibodies, and only 30% of patients with sicca had Sjögren antibodies. Autoantibodies were also relatively uncommon in patients with hepatitis (antinuclear antibody, 18%) and colitis (perinuclear antineutrophil cytoplasmic antibody, 19%). Some cohort studies analyzing pre-ICI seropositivity suggest there may be a role for autoantibodies as biomarkers of irAEs.

Conclusions

Reported autoantibody positivity is high in irAEs involving the endocrine organs, skin, and muscle, but lower in irAEs affecting other organ systems. Autoantibody investigations in pre-ICI treatment patients have yielded mixed results regarding their utility as a biomarker of irAEs.
How Deviation of Nasal Septum Affects Nasal Appearance in Unilateral Cleft Patients: A Study Using Cone-Beam Computed Tomography
Authors: Cao Haotian , Liu Xiao-Lin , Tsauo Chialing , Zheng Qian , Shi Bing , Wang Hu , Li Cheng-Hao
Published: August 2021

Aim:

To quantitatively evaluate the relationship between nasal appearance and nasal septum deviation in unilateral complete cleft patients using cone-beam computed tomography.

Method: Cone-beam computed tomography images of 180 patients with unilateral cleft lip/palate from June 2014 to June 2017 were used in the study. None of the subjects had undergone septoplasty. The data were compared between the 2 groups to elucidate the relationship between nasal appearance and deviated nasal septum in unilateral complete cleft patients.

Results:

The mean age of a total of 180 patients (126 males and 54 females) was 14.58 years, with a standard deviation of 7.10 years, ranged from 6 years old to 49 years old. Columella nasi symmetry parameters show slight positive significant association with angle of nasal septal deviation on transerve plan (r = 0.250, P < 0.001), TRSD (r = 0.323, P < 0.001) and coronal range of nasal septal deviation (r = 0.294, P < 0.001), and moderate positive significant association with coronal angle about septal deviation (r = 0.404, P < 0.001)

Conclusions:

Columella nasi symmetry affected by septal deviation, whereas there is lack of evidence to say symmetry of nasal tip and base affected by septal deviation. The symmetry of nasal tip and alar base are not just determined by nasal septum deviation. The nasal septum deviation show difference in different cleft type.
Cleft Nasal Stent Production Using Three-Dimensional Scanning and Printing Technology
Authors: Yeo Melissa , Por Yong Chen , Goh Aik Wei
Published: August 2021

In most cleft centers worldwide, nasal stents are routinely used in the postoperative period to prevent collapse of the lower lateral cartilage and maintain the shape of the nostrils as well as nasal alar. Prefabricated nasal stents are expensive and do not offer options for customization. In this paper, we introduce a cost-effective technique for manufacturing nasal stents using three-dimensional scanning and printing technology.
Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod
Authors: Alejevski Faredin , Leemans Michelle , Gaillard Anne-Laure , Leistenschneider David , de Flori Céline , Bougerol Marion , Le Mével Sébastien , Herrel Anthony , Fini Jean-Baptiste , Pézeron Guillaume , Tostivint Hervé
Published: August 2021

Urp1 and Urp2 are two neuropeptides of the urotensin II family identified in teleost fish and mainly expressed in cerebrospinal fluid (CSF)-contacting neurons. It has been recently proposed that Urp1 and Urp2 are required for correct axis formation and maintenance. Their action is thought to be mediated by the receptor Uts2r3, which is specifically expressed in dorsal somites. In support of this view, it has been demonstrated that the loss of
uts2r3
results in severe scoliosis in adult zebrafish. In the present study, we report for the first time the occurrence of
urp2,
but not of
urp1
, in two tetrapod species of the
Xenopus
genus. In
X. laevis
, we show that
urp2
mRNA-containing cells are CSF-contacting neurons. Furthermore, we identified
utr4,
the
X. laevis
counterparts of zebrafish
uts2r3,
and we demonstrate that, as in zebrafish, it is expressed in the dorsal somatic musculature. Finally, we reveal that, in
X. laevis,
the disruption of
utr4
results in an abnormal curvature of the antero-posterior axis of the tadpoles. Taken together, our results suggest that the role of the Utr4 signalling pathway in the control of body straightness is an ancestral feature of bony vertebrates and not just a peculiarity of ray-finned fishes.
Reducing false reassurance following negative results from asymptomatic coronavirus (Covid-19) testing: an online experiment
Authors: Batteux Eleonore , Bonfield Stefanie , Jones Leah Ffion , Carter Holly , Gold Natalie , Amlôt Richard , Marteau Theresa M. , Weston Dale
Published: August 2021

Objectives

Individuals who receive a negative lateral flow coronavirus (Covid-19) test result may misunderstand it as meaning ‘no risk of infectiousness’, giving false reassurance. This experiment tested the impact of adding information to negative test result messages about (a) residual risk and (b) need to continue protective behaviours.

Design

4 (residual risk) × 2 (post-test result behaviours) between-subjects design.

Setting

Online.

Participants

1200 adults from a representative UK sample recruited via Prolific (12-15 March 2021).

Interventions

Participants were randomly allocated to one of eight messages. Residual risk messages were: 1) ‘Your coronavirus test result is negative’ (control); 2) Message 1 plus ‘It’s likely you were not infectious when the test was done’ (Current NHS Test & Trace); 3) Message 2 plus ‘But there is still a chance you may be infectious’ (Elaborated NHS T&T); 4) Message 3 plus infographic depicting residual risk (Elaborated NHS T&T + infographic). Each message contained either no additional information or information about behaviour, i.e. the need to continue following guidelines and protective behaviours.

Outcome measures

(i) proportion understanding residual risk of infectiousness and (ii) likelihood of engaging in protective behaviours (score range 0-7).

Results

The control message decreased understanding relative to the current NHS T&T message: 54% vs 71% (AOR=0.37 95% CI [0.22, 0.61], p<.001). Understanding increased with the elaborated NHS T&T (89%; AOR=3.27 95% CI [1.78, 6.02], p<.001) and elaborated NHS T&T + infographic (91%; AOR=4.03 95% CI [2.14, 7.58], p<.001) compared to current NHS T&T message. Likelihood of engaging in protective behaviours was unaffected by information (F(1,1192)=0.43, p=.513), being high (M=6.4, SD=0.9) across the sample.

Conclusions

The addition of a single sentence (‘But there is still a chance you may be infectious’) to current NHS Test & Trace wording increased understanding of the residual risk of infection.

Trial registration

Open Science Framework: https://osf.io/byfz3/
Cryptic Transmission of the Delta Variant AY.3 Sublineage of SARS-CoV-2 among Fully Vaccinated Patients on an Inpatient Ward
Authors: Linsenmeyer Katherine , Gupta Kalpana , Madjarov Rebecca , Charness Michael E.
Published: August 2021

Background

Recent reports indicate that vaccination is effective in reducing symptomatic infection with the Delta variant of SARS-CoV-2 (DV) but is less protective against asymptomatic transmission of DV in outpatients than for earlier variants.

Here we report cryptic transmission associated with high DV viral load among vaccinated patients on an inpatient medical-surgical ward.

Methods

This observational study included all persons diagnosed with breakthrough SARS-CoV-2 infections at the VA Boston Healthcare System (VABHS) from March 11, 2021 to July 31, 2021, including those tested for surveillance, admission, symptoms, and as part of an outbreak investigation in July 2021. SARS-CoV-2 infection was diagnosed by reverse-transcription polymerase chain reaction (PCR) (Cepheid). Variants were identified by MassARRAY SARS-CoV-2 Variant Panel (36-plex PCR, Agena BioScience) for most breakthrough cases after June 2021 Viral genomic sequencing was performed by the Jackson Laboratory.

Results

An inpatient was diagnosed with asymptomatic DV infection on routine pre-discharge testing. Contact tracing detected infection in 6 of 38 patients (15.8%), 1 of 168 staff (0.6%), and 1 of 6 visitors (16.7%). Infection at the time of diagnosis was asymptomatic in 4 proximate, vaccinated patients, 1 vaccinated visitor, and 1 vaccinated employee caring for 1 undiagnosed, infected, vaccinated patient. Patients were unmasked, whereas staff wore surgical masks. PCR cycle threshold (Ct) for breakthrough infections indicated more than 1000-fold higher viral load for DV (Ct:21.7±4.3; n=15) than for earlier variants (Ct: 31.8±10.9, n=12; p=.003 (t-test)).

Conclusion

These findings demonstrate transmission of DV with high viral load between vaccinated inpatients, the continued efficacy of masking and vaccination for protecting healthcare personnel, and the potential need for post-admission surveillance to prevent cryptic DV transmission.
Time-to-event comparative effectiveness of NOACs vs VKAs in newly diagnosed non-valvular atrial fibrillation patients
Authors: Gallego Blanca , Zhu Jie
Published: August 2021

Abstract

Objective

To investigate the difference in the time-to-event probabilities of ischaemic events, major bleeding and death of NOAC vs VKAs in newly diagnosed non-valvular atrial fibrillation patients.

Design

Retrospective observational cohort study.

Setting

UK’s Clinical Practice Research Data linked to the Hospital Episode Statistics inpatient and outpatient data, mortality data and the Patient Level Index of Multiple Deprivation.

Participants

Patients over 18 years of age, with an initial diagnosis of atrial fibrillation between 1st-Mar-2011 and 31-July-2017, without a record for a valve condition, prosthesis or procedure previous to initial diagnosis, and without a record of oral anticoagulant treatment in the previous year.

Intervention

Oral anticoagulant treatment with either vitamin K antagonists (VKAs) or the newer target-specific oral anticoagulants (NOACs).

Main Outcome Measures

Ischaemic event, major bleeding event and death from 15 days from initial prescription up to two years follow-up.

Statistical Analysis

Treatment effect was defined as the difference in time-to-event probability between NOAC and VKA treatment groups. Treatment and outcomes were modelled using an ensemble of parametric and non-parametric models, and the average and conditional average treatment effects were estimated using one-step Targeted Maximum Likelihood Estimation (TMLE). Heterogeneity of treatment effect was examined using variable importance methods in Bayesian Additive Regression Trees (BART).

Results

The average treatment effect of NOAC vs VKA was consistently close to zero across all times, with a temporal average of 0.00[95%0.00, 0.00] for ischaemic event, 0.00%[95%−0.01, 0.01] for major bleeding and 0.00[95%−0.01, 0.01] for death. Only history of major bleeding was found to influence the distribution of treatment effect for major bleeding, but its impact on the associated conditional average treatment effect was not significant.

Conclusions

This study found no statistically significant difference between NOAC and VKA users up to two years of medication use for the prevention of ischaemic events, major bleeding or death.
Clenbuterol Attenuates Immune Reaction to Lipopolysaccharide and Its Relationship to Anhedonia in Adolescents
Authors: Nguyen Tram N. B. , Ely Benjamin A. , Pick Danielle , Patel Manishkumar , Xie Hui , Kim-Schulze Seunghee , Gabbay Vilma
Published: August 2021

While inflammation has been implicated in psychopathology, relationships between immune-suppressing processes and psychiatric constructs remain elusive. This study sought to assess whether β2-agonist clenbuterol (CBL) would attenuate immune activation in adolescents with mood and anxiety symptoms following ex vivo exposure of whole blood to lipopolysaccharide (LPS). Our focus on adolescents aimed to target a critical developmental period when psychiatric conditions often emerge and prior to chronicity effects. To capture a diverse range of immunologic and symptomatologic phenotypes, we included 97 psychotropic-medication free adolescents with mood and anxiety symptoms and 33 healthy controls. All participants had comprehensive evaluations and dimensional assessments of psychiatric symptoms. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, then analyzed for 41 cytokines, chemokines, and hematopoietic growth factors. Comparison analyses used Bonferroni-corrected nonparametric tests. Levels of nine immune biomarkers—including IL-1RA, IL-1β, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TGF-α, and TNF-α—were significantly reduced by CBL treatment compared to LPS alone. Exploratory factor analysis reduced 41 analytes into 5 immune factors in each experimental condition, and their relationships with psychiatric symptoms were examined as a secondary aim. CBL+LPS Factor 4—comprising EGF, PDGF-AA, PDGF-AB/BB, sCD40L, and GRO—significantly correlated with anticipatory and consummatory anhedonia, even after controlling for depression severity. This study supports the possible inhibitory effect of CBL on immune activation. Using a data-driven method, distinctive relationships between CBL-affected immune biomarkers and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.
Patient Informed Domain Adaptation Improves Clinical Drug Response Prediction
Authors: Anastopoulos Ioannis , Seninge Lucas , Ding Hongxu , Stuart Joshua
Published: August 2021

In-silico modeling of patient clinical drug response (CDR) promises to revolutionize personalized cancer treatment. State-of-the-art CDR predictions are usually based on cancer cell line drug perturbation profiles. However, prediction performance is limited due to the inherent differences between cancer cell lines and primary tumors. In addition, current computational models generally do not leverage both chemical information of a drug and a gene expression profile of a patient during training, which could boost prediction performance. Here we develop a Patient Adapted with Chemical Embedding (PACE) dual convergence deep learning framework that a) integrates gene expression along with drug chemical structures, and b) is adapted in an unsupervised fashion by primary tumor gene expression. We show that PACE achieves better discrimination between sensitive and resistant patients compared to the state-of-the-art linear regularized method (9/12 VS 3/12 drugs with available clinical outcomes) and alternative methods.
Enterococcus spp. have higher fitness for survival, in a pH-dependent manner, in pancreatic juice among duodenal bacterial flora
Authors: Itoyama Saki , Noda Emika , Takamatsu Shinji , Kondo Jumpei , Kawaguchi Rui , Shimosaka Munefumi , Fukuoka Tomoya , Motooka Daisuke , Nakamura Shota , Tanemura Masahiro , Mitsufuji Suguru , Iwagami Yoshifumi , Akita Hirofumi , Tobe Toru , Kamada Yoshihiro , Eguchi Hidetoshi , Miyoshi Eiji
Published: August 2021

Objectives

Bacterial infection is involved in the progression of many gastrointestinal diseases, including cancer; however, how and which bacteria colonize in pancreatic juice and tissue have yet to be elucidated. Recently, we reported that Enterococcus faecalis exists in the pancreatic juice and tissues of patients with chronic pancreatic disease. Here, we investigated the survival of E. faecalis in duodenal juice with different pH conditions.

Methods

Pancreatic juice samples from 62 patients with cancers of the duodeno-pancreato-biliary region were evaluated for the presence of E. faecalis. 16S ribosomal RNA PCR and 16S-based metagenome analyses were performed to determine the bacterial composition. The survival of E. faecalis in various pancreatic juice conditions was evaluated.

Results

Of 62 samples, 27% (17/62) were positive for Enterococcus spp., among which 71% (12/17) contained E. faecalis. Enterococcus spp. showed the highest fitness for survival in alkaline pancreatic juice among various bacterial species. The microbiome of pancreatic juice from patients with pancreatic and bile duct cancer showed diversity, but Enterococcus spp. were enriched among duodenal tumors and intraductal papillary mucinous neoplasms.

Conclusions

Alkalinity is important for the selective survival of E. faecalis among microbiota. E. faecalis may induce pancreatic inflammation with changes in pancreatic juice conditions.
A Tethered Ligand Assay to Probe SARS-CoV-2:ACE2 Interactions
Authors: Bauer Magnus S. , Gruber Sophia , Hausch Adina , Milles Lukas F. , Nicolaus Thomas , Schendel Leonard C. , López Navajas Pilar , Procko Erik , Lietha Daniel , Bernardi Rafael C. , Gaub Hermann E. , Lipfert Jan
Published: August 2021

SARS-CoV-2 infections are initiated by attachment of the receptor-binding domain (RBD) on the viral Spike protein to angiotensin-converting enzyme-2 (ACE2) on human host cells. This critical first step occurs in dynamic environments, where external forces act on the binding partners and multivalent interactions play critical roles, creating an urgent need for assays that can quantitate SARS-CoV-2 interactions with ACE2 under mechanical load and in defined geometries. Here, we introduce a tethered ligand assay that comprises the RBD and the ACE2 ectodomain joined by a flexible peptide linker. Using magnetic tweezers and atomic force spectroscopy as highly complementary single-molecule force spectroscopy techniques, we investigate the RBD:ACE2 interaction over the whole physiologically relevant force range. We combine the experimental results with steered molecular dynamics simulations and observe and assign fully consistent unbinding and unfolding events across the three techniques, enabling us to establish ACE2 unfolding as a molecular fingerprint. Measuring at forces of 2-5 pN, we quantify the force dependence and kinetics of the RBD:ACE2 bond in equilibrium. We show that the SARS-CoV-2 RBD:ACE2 interaction has higher mechanical stability, larger binding free energy, and a lower dissociation rate in comparison to SARS-CoV-1, which helps to rationalize the different infection patterns of the two viruses. By studying how free ACE2 outcompetes tethered ACE2, we show that our assay is sensitive to prevention of bond formation by external binders. We expect our results to provide a novel way to investigate the roles of mutations and blocking agents for targeted pharmaceutical intervention.
Adulthood Deficiency of the Insulin-like Growth Factor-1 Receptor in Hippocampal Neurons Impairs Cell Structure and Spatial Learning and Memory in Male and Not Female Mice
Authors: Hayes Cellas A. , Hodges Erik L. , Marshall Jessica P. , Logan Sreemathi , Farley Julie A. , Owens Daniel B. , Sonntag William E. , Ashpole Nicole M.
Published: August 2021

Reductions in insulin-like growth factor-1 (IGF-1) are associated with cognitive impairment and increased risk of neurodegenerative disease in advanced age. In mouse models, reduced IGF-1 early-in-life leads to memory impairments and synaptic dysfunction; however, these models are limited by systemic reductions in IGF-1. We hypothesized that IGF-1 continues to promote hippocampal neuron structure and function after development, and as such, the loss of IGF-1 signaling in adult neurons would lead to impaired spatial learning and memory. To test this, the IGF-1 receptor (IGF-1R) was genetically targeted in hippocampal neurons of adult male and female mice. Male mice deficient in neuronal IGF-1R exhibited spatial learning impairments as evidenced by increased pathlength and errors in the radial arm water maze. No differences in learning and memory were observed in female mice. Golgi-Cox staining revealed a reduced number of dendritic boutons of neurons the CA1 region of the hippocampus in male mice. Decreased MAPK and increased ROCK activity were also observed in these tissues. In vitro studies revealed that impaired neurite outgrowth due to inhibited IGF-1R signaling could be rescued by pharmacological inhibitors of ROCK. However, ROCK inhibition in neuronal IGF-1R-deficient mice did not fully rescue learning impairments or bouton numbers. Together, our study highlights that IGF-1 continues to support spatial learning and memory and neuronal structure in adulthood.
Professional Commitment and Its Associated Factors Among Institutional Delivery Services Providers In Public Health Facilities, In Shone District, Southern Ethiopia
Authors: Anshebo Melaku Wolde , Tessema Tesfaye Gobeana , Gebremariam Yosef Haile
Published: August 2021

Background

There is paucity of information on level of commitment among health professionals attending delivery service in public health facilities of low-income countries including Ethiopia.

Objective

To assess the level and factors associated with professional commitment among institutional delivery services providers at public health facilities in Shone District, Southern Ethiopia.

Methods

A facility-based cross-sectional study design was conducted at primary level public health facilities in Shone District. All health facilities (one primary hospital and 7 health centers) were included in the study. 503 study participants who fulfilled inclusion criteria in proportion to obstetric care providers in each public health facilities were selected by applying simple random sampling. Self-administered Likert scale type of questionnaire was used. Data were analyzed using SPSS version 20. Bivariate and multivariable logistic regression analyses were done to see the association between dependent and explanatory variables.

Results

The magnitude of professional commitment for obstetric care providers working in public health facilities of Shone district was 69.4%. In this study, those who worked at hospital, those who had positive attitude toward organizational commitment, and those who had positive attitude toward personal characteristics were 2.4, 2.3 and 1.76 times more likely committed to profession compared with the counterparts respectively.

Conclusion

The professional commitment among institutional delivery service provision was medium. All health professional should manage their own personal characteristics to behave in good way to be committed for their profession. Organizational commitment had great influence on professional commitment.
Use of health care services during the Covid-19 pandemic in Ethiopia: Evidence from a health facility survey
Authors: Shuka Zemzem Shigute , Mebratie Anagaw Derseh , Alemu Getnet , Rieger Matthias , Bedi Arjun Singh
Published: August 2021

Abstract
Introduction: In recent years Ethiopia has made enormous strides in enhancing access to health care, especially, maternal and child health care (MCH). With the onset and spread of Covid-19, the attention of the health care system has pivoted to handling the disease, potentially at the cost of other health care needs. This paper explores whether this shift has come at the cost of non Covid related health care, especially the use of MCH services.
Methods: Graphs, descriptive statistics and paired t-tests of significance are used to compare levels of inpatient and outpatient health care service utilization before and after the onset and spread of the virus. The analysis is based on a survey of 59 health centers and 29 public hospitals located in urban Ethiopia, the most acutely affected region of the country. Data on the use of health care services for a period of 24 months was gathered from the health management information systems (HMIS) of these facilities.
Results: There is a sharp reduction in the use of both inpatient (20-27%) and outpatient (27-34%) care, particularly in Addis Ababa, which has been most acutely affected by the virus. However, the decline does not come at the cost of MCH services. The use of several MCH components (skilled birth attendant deliveries, immunization, post-natal care) remains unaffected throughout the period while others (family planning services, ante-natal care) experience a decline (8-17%) in the immediate aftermath but recover soon after.
Conclusion: Concerns about the crowding out of MCH services due to the focus on Covid 19 are unfounded. Pro-active measures taken by the government and health care facilities to ring-fence the use of essential health care services have mitigated service disruptions. The results underline the resilience and agility displayed by one of the worlds most resource-constrained health care systems.
Observational study of HPV genitalia and oral infection in an unvaccinated population of men who have sex with men infected with HIV in Northwest Spain
Authors: Pérez-González Alexandre , Pérez Sonia , Carballo Raquel , López-Diez Elena , Limeres-Posse Jacobo , Ocampo Antonio
Published: August 2021

Background

Human papillomavirus (HPV) infection is the most common sexual transmitted disease (STD) and a risk factor for penile, oral and anal cancer. Human immunodeficiency virus (HIV) coinfection increases the risk of cancer. While HPV anal infection is well studied in men-who-have-sex-with-men (MSM), HPV genitalia and oral infection is less known.

Methods

This prevalence study of HPV infection in genitalia and oral cavity in HIV-MSM patients included 107 HPV non-vaccinated subjects. HPV-DNA was detected with Anyplex™ II HPV28 method. Participants completed a questionnaire on lifestyle and sexual behavior.

Results

Median age was 43 years (range 35-54 years); 97 patients were on antiretroviral treatment (ART); 81 (75.7%) had undetectable HIV-RNA; median CD4-lymphocyte count was 746 cell/mm3; 70 (65.4%) participants had a previous STD. HPV was detected in genitalia in 37 (34.6%) subjects; 26 (24.3%) in oral cavity and 12 (11.2%) in both locations. High-risk HPV genotypes were detected in 24 (22.4%) patients in genitalia and 15 (14%) in oral cavity.

Conclusions

HPV infection is common in unvaccinated HIV-MSM patients. Detectable HIV-RNA was associated with higher HPV prevalence in genitalia. High oncogenic risk HPV genotypes were more common in genitalia than in mouth.

Summary text

HPV infection is common in HIV infected subjects and it is a risk factor for many types of cancer. Although anal conduct is the most studied location, HPV can also infect genitalia and oral cavity. However, the frequency and distribution of HPV strains is different in both locations.
Lead-OR: A Multimodal Platform for Deep Brain Stimulation Surgery
Authors: Oxenford Simón , Roediger Jan , Milosevic Luka , Güttler Christopher , Spindler Philipp , Vajkoczy Peter , Neumann Wolf-Julian , Kühn Andrea , Horn Andreas
Published: August 2021

Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) can be used to match the neuroanatomy with expected neurophysiological activity patterns, commonly using up to five trajectories in parallel. However, understanding their location in relationship to basal ganglia anatomy can be challenging. Here we present a tool that integrates resources from stereotactic planning, neuroimaging, MER and high-resolution atlas data to create a real-time visualization of the implant trajectory. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present example use cases that demonstrate the functionality of the tool. The software toolbox is made openly available, extendable and holds translational potential in the field of stereotactic neurosurgery.
Quantitative Restoration of Immune Defense in Old Animals Determined by Naïve Antigen-Specific CD8 T cell Numbers
Authors: Uhrlaub Jennifer L. , Jergović Mladen , Bradshaw Christine M. , Sonar Sandip , Coplen Christopher P. , Dudakov Jarrod , Murray Kristy O. , Lanteri Marion C. , Busch Michael P. , van den Brink Marcel R. M. , Nikolich-Žugich Janko
Published: August 2021

Older humans and animals often exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naïve T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of West Nile virus (WNV) in both humans naturally exposed to, and mice experimentally infected with, WNV.

To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>four-fold) and NS4b:H-2Db-restricted antigen-specific CD8 T cells (two-fold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL-7C treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice and showed that injection of 5,400 (but not of 1,800 or 600) adult naïve WNV-specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms and are discussed in light of targets of immune reconstitution.