bluuebunny/crossref_metadata_2025 huggingface dataset:
Bluefin Larvae in Oligotrophic Ocean Foodwebs, investigations of nutrients to zooplankton: overview of the BLOOFINZ-Gulf of Mexico program
Authors: Gerard Trika , Lamkin John T , Kelly Thomas B , Knapp Angela N , Laiz-Carrión RaÚl , Malca Estrella , Selph Karen E , Shiroza Akihiro , Shropshire Taylor A , Stukel Michael R , Swalethorp Rasmus , Yingling Natalia , Landry Michael R
Published: July 2022

Western Atlantic bluefin tuna (ABT) undertake long-distance migrations from rich feeding grounds in the North Atlantic to spawn in oligotrophic waters of the Gulf of Mexico (GoM). Stock recruitment is strongly affected by interannual variability in the physical features associated with ABT larvae, but the nutrient sources and food-web structure of preferred habitat, the edges of anticyclonic loop eddies, are unknown. Here, we describe the goals, physical context, design and major findings of an end-to-end process study conducted during peak ABT spawning in May 2017 and 2018. Mesoscale features in the oceanic GoM were surveyed for larvae, and five multi-day Lagrangian experiments measured hydrography and nutrients; plankton biomass and composition from bacteria to zooplankton and fish larvae; phytoplankton nutrient uptake, productivity and taxon-specific growth rates; micro- and mesozooplankton grazing; particle export; and ABT larval feeding and growth rates. We provide a general introduction to the BLOOFINZ-GoM project (Bluefin tuna Larvae in Oligotrophic Ocean Foodwebs, Investigation of Nitrogen to Zooplankton) and highlight the finding, based on backtracking of experimental waters to their positions weeks earlier, that lateral transport from the continental slope region may be more of a key determinant of available habitat utilized by larvae than eddy edges per se.
On the Strict Majorant Property in Arbitrary Dimensions
Authors: Gressman P T , Guo S , Pierce L B , Roos J , Yung P -L
Published: July 2022

In this work we study d-dimensional majorant properties. We prove that a set of frequencies in $\mathbb{Z}^d$ satisfies the strict majorant property on $L^p([0,1]^d)$ for all p > 0 if and only if the set is affinely independent. We further construct three types of violations of the strict majorant property. Any set of at least d + 2 frequencies in $\mathbb{Z}^d$ violates the strict majorant property on $L^p([0,1]^d)$ for an open interval of $p \not\in 2\mathbb{N}$ of length 2. Any infinite set of frequencies in $\mathbb{Z}^d$ violates the strict majorant property on $L^p([0,1]^d)$ for an infinite sequence of open intervals of $p \not\in 2\mathbb{N}$ of length 2. Finally, given any p > 0 with $p \not\in 2\mathbb{N}$, we exhibit a set of d + 2 frequencies on the moment curve in $\mathbb{R}^d$ that violate the strict majorant property on $L^p([0,1]^d).$
An Inter-Comparison of Passive Dosemeters for Terrestrial Gamma Radiation Measurements
Authors: Ding Yanqiu , Wang Kaiyi , Gao Pin , Hu Aiying , Guo Wen , Han Yanqing
Published: July 2022

To evaluate the measurement method of passive dosemeters for terrestrial gamma radiation measurements. An inter-comparison of passive dosemeters for terrestrial gamma radiation measurements was organized alternately by the Japan Chemical Analysis Center, National Institute for Radiological Protection of Chinese Center for Disease Control and Prevention and Radiation Monitoring Technical Center of Ministry of Environmental Protection every 2 years. The procedures and exposure conditions of the field-exposure and reference irradiation test were provided by the organizer. During 2019–2020, the En values of Field-1 and Field-2 in three laboratories were lower than 1.0 and assigned ‘acceptable’ according to inter-comparison criteria. After the correction of the fading effect of dosemeter material, the En values of reference irradiation test (0.301 mGy, 1.000 mGy) in three laboratories were lower than 1.0 and assigned ‘acceptable’.
Jumping to Conclusions and Its Associations With Psychotic Experiences in Preadolescent Children at Familial High Risk of Schizophrenia or Bipolar Disorder-The Danish High Risk and Resilience Study, VIA 11
Authors: Gregersen Maja , Rohd Sinnika Birkehøj , Jepsen Jens Richardt Møllegaard , Brandt Julie Marie , Søndergaard Anne , Hjorthøj Carsten , Knudsen Christina Bruun , Andreassen Anna Krogh , Veddum Lotte , Ohland Jessica , Wilms Martin , Krantz Mette Falkenberg , Burton Birgitte Klee , Greve Aja , Bliksted Vibeke , Mors Ole , Clemmensen Lars , Nordentoft Merete , Thorup Anne Amalie Elgaard , Hemager Nicoline
Published: July 2022

Background

The jumping to conclusions (JTC) bias, ie, making decisions based on inadequate evidence, is associated with psychosis in adults and is believed to underlie the formation of delusions. Knowledge on the early manifestations of JTC and its associations with psychotic experiences (PE) in children and adolescents is lacking.

Design

Preadolescent children (mean age 11.9 y, SD 0.2) at familial high risk of schizophrenia (FHR-SZ, n = 169) or bipolar disorder (FHR-BP, n = 101), and controls (n = 173) were assessed with the Beads Task to examine JTC. The number of beads drawn before making a decision, “draws to decision” (DTD) was used as a primary outcome. PE were ascertained in face-to-face interviews. General intelligence was measured with Reynolds Intellectual Screening Test.

Results

Children at FHR-SZ took fewer DTD than controls (4.9 vs 5.9, Cohen’s d = 0.31, P = .004). Differences were attenuated when adjusting for IQ (Cohen’s d = 0.24, P = .02). Higher IQ was associated with a higher number of DTD (B = 0.073, P < .001). Current subclinical delusions compared with no PE were associated with fewer DTD in children at FHR-SZ (P = .04) and controls (P < .05). Associations between delusions and DTD were nullified when accounting for IQ.

Conclusions

JTC marks familial risk of psychosis in preadolescence, not reducible to general intelligence. JTC is associated with subclinical delusions, but this may be an expression of intellectual impairment. Future studies should establish temporality between JTC and delusion formation and examine JTC as a target for early intervention.
Bling-Bling politics: exposure to status-goods consumption shapes the social policy preferences of the less affuent
Authors: Lungu Laura Silvia
Published: July 2022

Consumer behavior and sociological research have recognized early on the negative externalities of exposure to conspicuous consumption: anxiety, debt and wasteful consumption. This article contributes to political economy by incorporating the costs of exposure to wealth-signaling consumption into the materialist self-interest model of social policy preferences. The argument is that exposure to conspicuous consumption reduces support for social spending and increases demand for lower income taxes. Tax cuts impact purchasing power directly, allowing individuals to keep up with consumption standards and to avoid looking poor by comparison. Two USA-based analyses using fine-grained data on consumption and individual attitudes at the zip code and county level support the argument. Importantly, less-affluent citizens are more likely to prioritize cuts to social spending over tax increases, at higher levels of conspicuous consumption. Additional analyses rule out alternative explanations like upward mobility prospects, local wealth effects and partisan context.
Ups and downs in finance, ups without downs in inequality
Authors: Godechot Olivier , Neumann Nils , Apascaritei Paula , Boza István , Hallsten Martin , Henriksen Lasse , Hermansen Are , Hou Feng , Jung Jiwook , Kodama Naomi , Křížková Alena , Lippényi Zoltán , Elvira Marta M , Melzer Silvia Maja , Mun Eunmi , Sabanci Halil , Soener Matthew , Thaning Max
Published: July 2022

The upswing in finance in recent decades has led to rising inequality, but do downswings in finance lead to a symmetric decline in inequality? We analyze the asymmetry of the effect of ups and downs in finance, and the effect of increased capital requirements and the bonus cap on national earnings inequality. We use administrative employer–employee-linked data from 1990 to 2019 for 12 countries and data from bank reports, from 2009 to 2017 in 13 European countries. We find a strong asymmetry in the effect of upswings and downswings in finance on earnings inequality, a weak, if any, mitigating effect of capital requirements on finance’s contribution to inequality, and a restructuring but no absolute effect of the bonus cap on financiers’ earnings. We suggest that while rising financiers’ wages increase inequality in upswings, they are resilient in downswings and thus downswings do not contribute to a symmetric decline in inequality.
‘Malaria Has Spoilt It’: Malaria, Neuropsychiatric Complications, and Insanity in ex-Servicemen in Post-First World War Britain
Authors: Fantauzzo Justin
Published: July 2022

This article focuses on the cases of two British ex-servicemen who contracted malaria during or immediately after the First World War, were charged with murder in the 1920s, and pled insanity due to their malaria and long-term neuropsychiatric complications. One was found ‘guilty but insane’ and committed to Broadmoor Criminal Lunatic Asylum in June 1923, while the other was convicted and hanged in July 1927. It argues that, at a time when the medical community sought out the causes of mental disease in the physical body, medico-legal arguments about malaria and insanity were received inconsistently by inter-war British courts. Class, education, social status, institutional support and the nature of the crime all mattered, as they had in the diagnoses, treatment and trials of other ex-servicemen with psychiatric illnesses.
“We Got Witnesses” Black Women’s Counter-Surveillance for Navigating Police Violence and Legal Estrangement
Authors: Gonzalez Shannon Malone , Deckard Faith M
Published: July 2022

Police violence shapes the lives of racial and ethnic minorities, and while much has been written about strategic responses to police, missing is an examination of how black women navigate interactions with officers. Based on 32 interviews with black women, we find that they use witnessing, or the mobilization of others as observers to police encounters. Research demonstrates the rising role of videos and smartphones in documenting encounters with officers. We find that black women adapt witnessing techniques based on their surroundings, available resources, and network contacts. Three forms of witnessing are observed: physical witnessing, mobilizing others in close proximity to interactions with officers; virtual witnessing, using cellphone or social media technology to contact others or record interactions with officers; and institutional witnessing, leveraging police or other institutional contacts as interveners to interactions with officers. Black women mobilize witnessing to deescalate violence, gather evidence, and promote accountability. Attuned to both the interactional and structural dynamics of police encounters, black women conceptualize witnessing as a way to survive police encounters and navigate their legal estrangement within the carceral system. We theorize black women’s witnessing as a form of resistance as they work to reconfigure short- and long-term power relations between themselves, their communities, and police.
Tree organ growth and carbon allocation dynamics impact the magnitude and δ13C signal of stem and soil CO2 fluxes
Authors: Tang Yu , Schiestl-Aalto Pauliina , Saurer Matthias , Sahlstedt Elina , Kulmala Liisa , Kolari Pasi , Ryhti Kira , Salmon Yann , Jyske Tuula , Ding Yiyang , Bäck Jaana , Rinne-Garmston Katja T
Published: July 2022

Incomplete knowledge of carbon (C) allocation dynamics in trees hinders accurate modeling and future predictions of tree growth. We studied C allocation dynamics in a mature Pinus sylvestris L. dominated forest with a novel analytical approach, allowing the first comparison of: (i) magnitude and δ13C of shoot, stem and soil CO2 fluxes (Ashoot, Rstem and Rsoil), (ii) concentration and δ13C of compound-specific and/or bulk non-structural carbohydrates (NSCs) in phloem and roots and (iii) growth of stem and fine roots. Results showed a significant effect of phloem NSC concentrations on tracheid growth, and both variables significantly impacted Rstem. Also, concentrations of root NSCs, especially starch, had a significant effect on fine root growth, although no effect of root NSC concentrations or root growth was detected on Rsoil. Time series analysis between δ13C of Ashoot and δ13C of Rstem or δ13C of Rsoil revealed strengthened C allocation to stem or roots under high C demands. Furthermore, we detected a significant correlation between δ13C of Rstem and δ13C of phloem sucrose and glucose, but not for starch or water-soluble carbohydrates. Our results indicate the need to include C allocation dynamics into tree growth models. We recommend using compound-specific concentration and δ13C analysis to reveal C allocation processes that may not be detected by the conventional approach that utilizes bulk organic matter.
Ethical Issues in the US 1956 National Academy of Sciences BEAR I Genetics Panel Report to the Public
Authors: Calabrese Edward J. , Giordano James
Published: July 2022

This paper presents newly discovered evidence from the personal correspondence of four US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) Genetics Panelists that their 1956 report to the public was written by a third party and was neither reviewed nor approved by the Panel prior to its publication and release to the public. The letters revealed that the 1956 Report contained serious errors and did not represent the views of the Panel. The failure of the US NAS to notify the public that the Report had not been reviewed and approved by the Panel represents a serious breach of ethics. Further ethical issues relate to the failure of the NAS to (1) correct the errors in the Report within an appropriately timely manner and (2) reveal the lack of approval by the Panel even after the Report’s release. In light of these discoveries and the profound historical—and continuing—significance of the 1956 Report to all conventional cancer-related risk assessment processes, we opine that this ethical improbity must be acknowledged and that this document must be retracted by the NAS.
Case Report: Acute Retinal Necrosis after a Cervical Epidural Steroid Injection
Authors: Kamo Samantha F. , Tran Nina T. , Marquez Mark A.
Published: July 2022

SIGNIFICANCE

Acute retinal necrosis is a rare, sight-threatening condition typically found in immunocompromised patients and is most commonly caused by varicella zoster virus. Because of the poor prognosis and rapid progression of the disease course, prompt antiviral management is paramount.

PURPOSE

A case report of acute retinal necrosis in a patient with herpes virus infection after a cervical epidural corticosteroid injection was performed. Extensive laboratory work and frequent follow-ups are necessary for management. This case report outlines the clinical signs of acute retinal necrosis and discusses the appropriate referrals and treatment needed to improve prognosis.

CASE REPORT

A 63-year-old man presented to our eye clinic with symptoms of pain and light sensitivity. Examination revealed anterior uveitis, vitritis, optic disc edema, macular edema, vasculitis, and retinitis of the left eye. The serum antibody test results showed abnormal ranges for varicella zoster virus and herpes simplex virus type 1, and the patient was diagnosed with acute retinal necrosis. Treatment prescribed by a retina specialist included oral valacyclovir and later oral prednisolone, for which the patient responded well before developing the common complication of retinal detachment.

CONCLUSIONS

The progressive nature of acute retinal necrosis is usually debilitating to vision, even when managed properly. Because prognosis is often poor, it is important to make proper diagnoses combined with a complete review of the patient's medical history and immune status to prevent further vision loss.
Effect of aging on immune cells in male HIV-infected and -uninfected healthy individuals
Authors: Rai M. Ali , Shi Victoria , Kennedy Brooke D. , Whitehead Emily J. , Justement Jesse S. , Paul Subrata , Blazkova Jana , Chun Tae-Wook
Published: July 2022

Objective:

HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8+ T cells of age-matched HIV-infected and -uninfected male participants.

Design:

Levels of immune activation and exhaustion markers on peripheral blood CD8+ T cells of HIV-infected and -uninfected participants were examined.

Methods:

110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8+ T cells of the study participants were determined by flow cytometry.

Results:

The level of TIGIT on CD8+ T cells was higher in aviremic HIV-infected compared to uninfected participants (P < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8+ T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT+ and CD38+CD8+ T cells in both groups; however, no correlation was found between age and the level of PD-1+CD8+ T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8+ T cells.

Conclusions:

The findings of our study highlight the role of aging in the expression of immune markers on CD8+ T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals.
Immune recovery-related patterns of post kala-azar dermal and ocular leishmaniasis in people living with HIV
Authors: Rousset Stella , Zenou Mathilde , Saunier Aurélie , Varenne Fanny , Soler Vincent , Tournier Emilie , Legrand Léa , Lachaud Laurence , Buffet Pierre , Berry Antoine , Delobel Pierre , Martin-Blondel Guillaume
Published: July 2022

Objective:

Post kala-azar dermal leishmaniasis (PKDL) is a rare complication of visceral leishmaniasis. We aimed at reporting PKDL cases in people living with HIV (PLHIV) and compare their characteristics based on whether PKDL occurred in the context of immune recovery under antiretroviral therapy (ART) or not.

Design:

National survey and literature review.

Methods:

We called for observations in France in October 2020 and performed a literature review from PubMed (Medline) and Web of Science up to December 2020. Two groups of patients were defined based on whether PKDL occurred in the context of immune recovery under ART (group 1) or not (group 2), and compared.

Results:

Three PLHIV with PKDL identified in France in the last decade were described and added to 33 cases from the literature. Compared with group 2 (16/36, 44.4%), patients from group 1 (20/36, 55.6%) originated more frequently from Europe (12/20, 60% vs. 2/16, 12.5%; P = 0.0038), had higher median blood CD4+ cell counts (221/μl vs. 61/μl; P = 0.0005) and increase under ART (122/μl, interquartile range 73–243 vs. 33/μl, interquartile range 0–53; P = 0.0044), had less frequently concomitant visceral leishmaniasis (3/20, 15% vs. 8/12, 66.7%; P = 0.006), and a trend to more frequent ocular involvement (7/20, 35% vs. 1/16, 6.25%; P = 0.0531).

Conclusion:

In PLHIV, PKDL occurs after a cured episode of visceral leishmaniasis as part of an immune restoration disease under ART, or concomitant to a visceral leishmaniasis relapse in a context of AIDS. For the latter, the denomination ‘disseminated cutaneous lesions associated with visceral leishmaniasis’ seems more accurate than PKDL.
Prevention of SARS-CoV-2 and respiratory viral infections in healthcare settings: current and emerging concepts
Authors: Rhee Chanu , Baker Meghan A. , Klompas Michael
Published: July 2022

Purpose of review

COVID-19 has catalyzed a wealth of new data on the science of respiratory pathogen transmission and revealed opportunities to enhance infection prevention practices in healthcare settings.

Recent findings

New data refute the traditional division between droplet vs airborne transmission and clarify the central role of aerosols in spreading all respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), even in the absence of so-called ’aerosol-generating procedures’ (AGPs). Indeed, most AGPs generate fewer aerosols than talking, labored breathing, or coughing. Risk factors for transmission include high viral loads, symptoms, proximity, prolonged exposure, lack of masking, and poor ventilation. Testing all patients on admission and thereafter can identify early occult infections and prevent hospital-based clusters. Additional prevention strategies include universal masking, encouraging universal vaccination, preferential use of N95 respirators when community rates are high, improving native ventilation, utilizing portable high-efficiency particulate air filters when ventilation is limited, and minimizing room sharing when possible.

Multifaceted infection prevention programs that include universal testing, masking, vaccination, and enhanced ventilation can minimize nosocomial SARS-CoV-2 infections in patients and workplace infections in healthcare personnel. Extending these insights to other respiratory viruses may further increase the safety of healthcare and ready hospitals for novel respiratory viruses that may emerge in the future.
Adjuvanted recombinant zoster vaccine in solid organ transplant and hematopoietic stem-cell transplant recipients
Authors: Provost-Olewczynska Jean-Xavier , Eberhardt Christiane Sigrid
Published: July 2022

Purpose of review

Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance.

Recent findings

Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations.

Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients.
Postpancreatectomy Acute Pancreatitis After Pancreaticoduodenectomy
Authors: Chen Haoda , Wang Chao , Shen Ziyun , Wang Weishen , Weng Yuanchi , Ying Xiayang , Deng Xiaxing , Shen Baiyong
Published: July 2022

Objective:

This study aimed to characterize postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD) in a high-volume center.

Background:

The International Study Group for Pancreatic Surgery (ISGPS) has recently proposed a new definition and grading scale of PPAP, but specific studies are lacking.

Methods:

Patients who underwent PD from 2020 to 2021 were retrospectively reviewed. PPAP was defined based on the International Study Group for Pancreatic Surgery definition: sustained elevation of serum amylase levels for least the first 48 hours postoperatively and radiologic alterations consistent with PPAP.

Results:

Among a total of 716 patients who were finally analyzed, PPAP occurred in 152 (21.2%) patients. Patients with PPAP were associated with significantly higher incidences of postoperative pancreatic fistula (POPF) (40.8% vs 11.7%, P<0.001), major complications (13.8% vs 6.6%, P=0.004), and biliary leak (11.8% vs 4.6%, P=0.001). Among them, 8 patients developed grade C PPAP leading to organ failure, reoperation, or death. Patients developing PPAP alone also demonstrated a statistically significantly increased rate of major complications than those without PPAP or POPF. In contrast, no differences were found in postoperative outcomes in patients with POPF in terms of whether they were associated with PPAP.

Conclusion:

PPAP is a distinct complication after PD with distinctive clinical outcomes. A part of PPAP presents as an inflammatory process in the early postoperative period but sometimes could lead to necrotizing pancreatitis or other severe clinical scenarios, and another part of PPAP would lead to anastomotic failure that accounts for a great proportion of POPF occurrence.
Current Status of ABO-incompatible Liver Transplantation
Authors: Egawa Hiroto , Ohdan Hideki , Saito Kazuhide
Published: July 2022

By 2014, strategies to prevent antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) were established in Japan and expanded primarily to Asia, where LDLT is now the predominant form of LT owing to the scarcity of brain-dead donors. A desensitization protocol consisting of rituximab (375 mg/m2), plasma pheresis, tacrolimus, and mycophenolate mofetil before LDLT, followed by standard immunosuppression, is currently the best option in terms of safety and efficacy. Rituximab administration is now known not to increase the risk of hepatocellular carcinoma recurrence, and the feasibility of rituximab for LDLT for acute liver failure and the need for desensitization before LDLT in children older than 1 y have been documented. Strategies are needed to distinguish patients at high risk of AMR from those at low risk and to adjust immunosuppression to prevent both AMR and infection. Specific single-nucleotide polymorphisms in genes encoding Fcγ receptors affecting the cytotoxicity of rituximab on B cells could be useful for adjusting immunosuppression levels to decrease infectious complications. Immunological accommodation after ABO-I transplantation could be provided by immune factors in both the grafts and recipients.
Prolyl Hydroxylase Inhibition Mitigates Allograft Injury During Liver Transplantation
Authors: Harnoss Jonathan M. , Cai Jun , Hinterkopf Sascha , Radhakrishnan Praveen , Schmitt Annabelle , Dupovac Mareen , Nees Lisa K. , Strowitzki Moritz J. , Taylor Cormac T. , Schneider Martin
Published: July 2022

Background.

Ischemia and reperfusion injury (IRI) determines primary allograft function after liver transplantation (LT). Primary graft dysfunction (PGD) is associated with increased morbidity and impaired graft survival and can eventually progress to graft failure requiring retransplantation. Hypoxia-inducible transcription factor–prolyl hydroxylase containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors, which control the adaptive hypoxia response through the hypoxia-inducible factor (HIF). In this study, we have investigated pharmacological activation of the HIF pathway through inhibition of PHDs as a strategy to reduce PGD after LT.

Methods.

Primary rat hepatocytes were isolated and the impact of the pan-PHD small-molecule inhibitor ethyl-3,4-dihydroxybenzoate (EDHB) on HIF-1 and its downstream target gene expression assessed. Subsequently, various rodent models of segmental warm liver ischemia and reperfusion and orthotopic LT were applied to study the impact of EDHB on normothermic or combined cold and warm liver IRI. Liver enzyme levels and histology were analyzed to quantify hepatic IRI.

Results.

In vitro, EDHB induced HIF-1 signaling and significantly upregulated its downstream target heme-oxygenase 1 in primary rat hepatocytes. In vivo, after establishment of the optimal EDHB pretreatment conditions in a murine IRI model, EDHB pretreatment significantly mitigated hepatic IRI after warm segmental liver ischemia and reperfusion and allograft injury after orthotopic LT in rats. Mechanistically, EDHB stabilized HIF-1 in the liver and subsequently increased hepatoprotective heme-oxygenase 1 levels, which correlated with reduced hepatic IRI in these models.

Conclusions.

This proof-of-concept study establishes a strong therapeutic rationale for targeting PHDs with small-molecule inhibitors to mitigate PGD after LT.
On non-locally elastic Rayleigh wave
Authors: Kaplunov J. , Prikazchikov D. A. , Prikazchikova L.
Published: July 2022

The Rayleigh-type wave solution within a widely used differential formulation in non-local elasticity is revisited. It is demonstrated that this wave solution does not satisfy the equations of motion for non-local stresses. A modified differential model taking into account a non-local boundary layer is developed. Correspondence of the latter model to the original integral theory with the kernel in the form of the zero-order modified Bessel function of the second kind is addressed. Asymptotic behaviour of the model is investigated, resulting in a leading-order non-local correction to the classical Rayleigh wave speed due to the effect of the boundary layer. The suitability of a continuous set-up for modelling boundary layers in the framework of non-local elasticity is analysed starting from a toy problem for a semi-infinite chain.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Metamaterial shields for inner protection and outer tuning through a relaxed micromorphic approach
Authors: Rizzi Gianluca , Neff Patrizio , Madeo Angela
Published: July 2022

In this paper, a coherent boundary value problem to model metamaterials' behaviour based on the relaxed micromorphic model is established. This boundary value problem includes well-posed boundary conditions, thus disclosing the possibility of exploring the scattering patterns of finite-size metamaterial specimens. Thanks to the simplified model’s structure (few frequency- and angle-independent parameters), we are able to unveil the scattering metamaterial’s response for a wide range of frequencies and angles of propagation of the incident wave. These results are an important stepping stone towards the conception of more complex large-scale meta-structures that can control elastic waves and recover energy.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
An exploration of the genetics of the mutant Huntingtin (mHtt) gene in a cohort of patients with chorea from different tribes in 6 sub-Saharan African countries
Authors: Muthinja Mendi J , Guelngar Carlos Othon , Fall Maouly , Jama Fatumah , Shuja Huda Aldeen , Nambafu Jamila , Bocoum Abdoulaye , Massi Daniel Gams , Ojo Oluwadamilola O. , Okubadejo Njideka U. , Taiwo Funmilola Tolulope , Diop Alassane Mamadou , De Chacus Coudjou J.D.G. , Cissé Fodé Abass , Cissé Amara , Hooker Juzar , Sokhi Dilraj , Houlden Henry , Rizig Mie
Published: July 2022

Background

Africans are underrepresented in Huntington’s disease research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent, however recent work has shown the existence of a unique Huntingtin haplotype in South-Africa specific to indigenous Africans.

Objective

We aimed to investigate the CAG repeats expansion in the Huntingtin (Htt) gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa.

Methods

We evaluated 104 participants: 45 patients with chorea, 24 asymptomatic first-degree relatives of subjects with chorea and 35 healthy controls for the presence of the mHtt. Participants were recruited from 6 African countries. Additional data were collected from patients positive for the mHtt including demographics, presence of psychiatric and cognitive symptoms, family history, spoken languages and tribal origin. Additionally, their pedigrees were examined to estimate the number of people at risk of developing HD and to trace back the earliest account of the disease in each region.

Results

HD cases were identified in all countries. 53.3% of patients with chorea were carriers for the mHTT; median tract size 45 CAG repeats. Of the asymptomatic relatives 41.6% were carriers for the mHTT; median tract size 42.5 CAG. No homozygous carries were identified. Median CAG tract size in controls was 17 CAG repeats. Men and women were equally affected by HD. All patients with HD—bar three who were juvenile onset of <21 years—were defined as adult onset (median age of onset 40 years). HD transmission followed an autosomal dominant pattern in 80% (16/20) of HD families. In familial cases, maternal transmission was higher (56%) than paternal transmission (44%). The number of asymptomatic individuals at risk of developing HD was estimated at 10 times more than the symptomatic patients. HD could be traced back to the early 1900s in most African sites. HD cases spread over 8 tribes belonging to two distinct linguistic lineages separated from each other approximately 37 kya ago: Nilo-Sahara and Niger-Congo.

Conclusion

This is the first study examining HD in multiple sites in sub-Saharan Africa. We demonstrated that HD is found in multiple tribes residing in 6 sub-Saharan African countries including the first genetically confirmed HD cases from Guinea and Kenya. The prevalence of HD in the African continent, its associated socio-economic impact, and genetic origins need further exploration and reappraisal.
Loss of SARS-CoV-2 Seropositivity among Healthy Young Adults over Seven Months
Authors: Lea C. Suzanne , Simeonsson Kristina , Kipp Aaron , McNeill Charleen , Wilcox Lisa , Irish William , Morris Hannah , Diaz Omar , Fallon John , Roper Rachel L.
Published: July 2022

Objective

We conducted a longitudinal study to estimate immunity produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among university students over seven months.

Methods

All participants were attending a public university and resided in Pitt County, North Carolina. University students enrolled weekly for 10 weeks between August 26, 2020 and October 28, 2020, resulting in 136 young adults completing at least one study visit by November 17, 2020. Enrolled students completed an online survey and nasal swab collection at two week intervals and monthly blood collection between August 26, 2020 and March 31, 2021.

Results

Amongst 695 serum samples tested during follow-up, the prevalence of a positive result for anti-nucleocapsid antibodies (N-IgG) was 9.78%. In 22 students with more than one positive N-IgG serum sample, 68.1% of group had decline of N-IgG below positive threshold over 140 days. Anti-spike antibodies were detected in all 11 vaccinated students who were vaccinated during March 2021.

Conclusions

In healthy young adults, N-IgG wanes below detectable threshold within five months. S-IgG remained consistently elevated months after infection, and significantly increased after vaccination.
Wheat cells show positional responses to invasive Zymoseptoria tritici
Authors: Valente Francesco , Mansfield Jessica , Herring Daniel , Romana Giuseppe , Rodrigues Cecilia , Metz Jeremy , Craze Melanie , Bowden Sarah , Greenland Andy , Moger Julian , Haynes Ken , Richards David M. , Wallington Emma , Deeks Michael J.
Published: July 2022

The stomatal complex of grasses consists of two guard cells and two adjacent subsidiary cells that cooperate during stomatal closure. Zymoseptoria tritici, the main causal agent of Septoria tritici blotch in wheat, enters the host via stomata. Here we test the hypothesis that the stomatal complex shows focused sub-cellular responses to invading Z. tritici hyphae.

We have combined live-cell transmission light microscopy, immunofluorescence and CRS microscopy to identify cell wall modifications triggered by hyphal invasion. Furthermore, we have used confocal fluorescence microscopy and automated quantitative image analysis to assess whether host cells respond to hyphae through spatial redistribution of organelles.

We find that subsidiary cells construct papillae that are accurately aligned with hyphal position even when hyphae are occluded by guard cells. These are distinct from those induced by powdery mildew, with callose restricted to a crust that surrounds content with a high-amplitude Raman signal in the CH-band. Peroxisome populations in subsidiary cells show distributions with modes weakly correlated with hyphal position but do not differ significantly between compatible and incompatible interactions.

Our data suggest local changes to cell wall architecture and focal accumulation of organelles in subsidiary cells could play roles in crop defence during host leaf penetration by Z. tritici. Molecular strategies to amplify these responses may provide novel routes for crop protection.
Cryptochrome Stabilization Ameliorates Chronic Pain
Authors: Wei L. , Wu Y. , Zirpel F. , Flower G. , Vierbergen J. V , Wieser V. , Peirson S. , Sleven H. , Pokhilko A. , Cader M. Z.
Published: July 2022

Physiological and pathological pain exhibits striking diurnal variation, but the underlying mechanisms are largely unknown. We now describe an independent molecular clock in peripheral sensory neurons and satellite glial cells of sensory ganglia. We show that it is the sensory neuron transcription-translation feedback loops (TTFLs) that are responsible for diurnal pain behaviors. This clock regulates diurnal neurophysiological responses to a range of ligands, as well as synaptic activities of primary nociceptors. Furthermore, we find that loss of Cry1 and Cry2, the repressive arm of the core TTFLs, intensifies pain responses associated with increased voltage-gated sodium channel currents. Conversely, stabilization of CRY1 and CRY2 using the small molecule KL001, reduces pain sensitivity. Our results highlight novel opportunities to address chronic pain by directly harnessing circadian mechanisms.

One-Sentence Summary

A peripheral pain clock governs daily pain fluctuations, which can be harnessed for treating pain disorders.
In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya
Authors: Thottappillil Anjana , Sahoo Sthitaprajna , Chakraborty Abhijnan , Kouser Sania , Ravi R. Vidhya , Garawadmath Soumya , Banvi Pranav Girish , Kukkupuni Subrahmanya Kumar , Mohan S Suma , Vishnuprasad Chethala N
Published: July 2022

Frontiers of disease biology started recognizing the importance of systems and network medicine approach for managing chronic disease like diabetes. Dipeptidyl-peptidase IV (DPP4) inhibitors are one such class of anti-diabetic drugs recognized for their systemic biological actions. Polyherbal preparations likeAyurvedaformulations are ideal for identifying novel DPP4 inhibitors having greater efficacy and safety profile. Additionally, expanding the research on the multitargeted mode of action of these polyherbal formulations can render novel insights into the complex biology of disease manifestations. The current study aims at identifying DPP4 inhibitory potential of a clinically established Ayurveda anti-diabetic formulationNisakathakadi Kashaya(NK) usingin vitroandin silicomethods as well as the modulation of diabetes associated gene network by NK. a. Standard enzyme inhibition assay was used to study the DPP4 inhibitory potential of NK, followed by bioinformatics and computational biology tools for identifying the potential bioactives and their molecular interactions involved in DPP4 inhibition. STITCH, CHEMBL and BindingDB databases were used for target mapping and depicting the multi-targeted network pharmacology interaction of NK and the formulation. EnrichR was used to depict a sub-network of diabetes proteins and their relationship with diabetes associated comorbidities. NK demonstrated a dose dependent DPP4 inhibition with an IC50of 2.06 μg GAE/mL. Molecular docking identified three compounds namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose showing stable interactions with DPP4 similar to the standard drug Vildagliptin. The network pharmacology analysis of NK identified a number of targets like TNFα, TGFβ1, SOD1, SOD2, AKT1, DPP4 and GLP1R in its protein-protein interaction network which are vital to diabetic progression and complications. The present work demonstrated that the polyherbal formulation NK has DPP4 inhibition potential and modulates a large number of diabetes related proteins and pathways. The approach adopted in the current study by combiningin vitroandin silicomethods allowed us to understand the mechanism of DPP4 inhibition by the formulation and also the possible pharmacological networking through which the formulation exert its systemic effect in diabetes management.
Effects of environmental manipulations on cocaine-vs-social choice in male and female rats
Authors: Marcus Madison M. , Negus S. Stevens , Banks Matthew L.
Published: July 2022

Cocaine use disorder occurs in an environment where cocaine and other nondrug commodities are concurrently available. Preclinical drug-vs-nondrug choice procedures are one simplified method of modeling this complex clinical environment. The present study established a discrete-trial progressive-ratio (PR) cocaine-vs-social interaction choice procedure in male and female rats and determined sensitivity of choice behavior to manipulations of reinforcer magnitude and non-contingent “sample” reinforcer presentation. Rats could make up to nine discrete choices between an intravenous cocaine infusion (0.1 – 1.0 mg/kg/inf) and social interaction with a same-sex social “Partner” rat. Cocaine infusions were available under a PR schedule of reinforcement, and social interaction was available under a fixed-ratio (FR) 3 schedule. Social interaction was chosen over no or small cocaine doses (saline, 0.01 mg/kg/inf) and behavior was reallocated away from social and towards cocaine at larger cocaine doses (1.0 mg/kg/inf). Manipulating social interaction time as one method to alter social reinforcer magnitude did not significantly alter cocaine-vs-social choice. Removing the non-contingent reinforcer presentations before the discrete choice trials also failed to affect cocaine-vs-social choice, suggesting the time interval was sufficient to minimize any potential influence of the non-contingent cocaine infusions on subsequent choice behavior. Overall, the present results were consistent with previous drug-vs-social choice studies and extend our knowledge of environmental factors impacting drug-vs-social choice. Future studies determining the pharmacological sensitivity of cocaine-vs-social choice will be important in expanding the preclinical utility of these procedures for candidate medication drug development.
A community driven GWAS summary statistics standard
Authors: Hayhurst James , Buniello Annalisa , Harris Laura , Mosaku Abayomi , Chang Christopher , Gignoux Christopher R. , Hatzikotoulas Konstantinos , Karim Mohd Anisul , Lambert Samuel A. , Lyon Matt , McMahon Aoife , Okada Yukinori , Pirastu Nicola , Rayner N. William , Schwartzentruber Jeremy , Vaughan Robert , Verma Shefali , Wilder Steven P. , Cunningham Fiona , Hindorff Lucia , Wiley Ken , Parkinson Helen , Barroso Inês
Published: July 2022

Summary statistics from genome-wide association studies (GWAS) represent a huge potential for research. A challenge for researchers in this field is the access and sharing of summary statistics data due to a lack of standards for the data content and file format. For this reason, the GWAS Catalog hosted a series of meetings in 2021 with summary statistics stakeholders to guide the development of a standard format. The key requirements from the stakeholders were for a standard that contained key data elements to be able to support a wide range of data analyses, required low bioinformatics skills for file access and generation, to have easily accessible metadata, and unambiguous and interoperable data. Here, we define the specifications for the first version of the GWAS-SSF format, which was developed to meet the requirements discussed with the community. GWAS-SSF consists of a tab-separated data file with well-defined fields and an accompanying metadata file.
Rarity: Discovering rare cell populations from single-cell imaging data
Authors: Märtens Kaspar , Bortolomeazzi Michele , Montorsi Lucia , Spencer Jo , Ciccarelli Francesca , Yau Christopher
Published: July 2022

Background

Cell type identification plays an important role in the analysis and interpretation of single-cell data and can be carried out via supervised or unsupervised clustering approaches. Supervised methods are best suited where we can list all cell types and their respective marker genes a priori. While unsupervised clustering algorithms look for groups of cells with similar expression properties. This property permits the identification of both known and unknown cell populations, making unsupervised methods suitable for discovery.. Success is dependent on the relative strength of the expression signature of each group as well as the number of cells. Rare cell types therefore present a particular challenge that are magnified when they are defined by differentially expressing a small number of genes. Typical unsupervised approaches fail to identify such rare subpopulations, and these cells tend to be absorbed into more prevalent cell types.

Results

In order to balance these competing demands, we have developed a novel statistical framework for unsupervised clustering, named Rarity, that enables the discovery process for rare cell types to be more robust, consistent and interpretable. We achieve this by devising a novel clustering method based on a Bayesian latent variable model in which we assign cells to inferred latent binary on/off expression profiles. This lets us achieve increased sensitivity to rare cell populations while also allowing us to control and interpret potential false positive discoveries.

Conclusions

We systematically study the challenges associated with rare cell type identification and demonstrate the utility of Rarity on various IMC data sets.