bluuebunny/crossref_metadata_2025 huggingface dataset:
Late offspring effects of antenatal thyroid screening
Authors: Panagiotou Grigorios , Taylor Peter N , Rees D Aled , Okosieme Onyebuchi E
Published: July 2022

Background

Thyroid dysfunction in pregnancy is associated with adverse offspring outcomes and recent birth-cohort studies suggest that even mild degrees of thyroid dysfunction may be linked with a range of late cognitive and behavioural effects in childhood and adolescence.

Sources of data

This review summarizes recent literature of observational studies and critically appraises randomized controlled trials (RCTs) of antenatal thyroid screening and Levothyroxine intervention.

Areas of agreement

Overt hypothyroidism and hyperthyroidism carry significant risks for unfavourable offspring outcomes and should be appropriately corrected in pregnancy.

Areas of controversy

The significance of subclinical hypothyroidism and hypothyroxinaemia is still unclear. Meta-analyses of birth-cohort studies show associations of maternal subclinical hypothyroidism and hypothyroxinaemia with intellectual deficits, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders, while hyperthyroidism and high-normal FT4 were linked with ADHD. RCTs have shown no benefits of screening on neurodevelopmental outcomes although Levothyroxine could have been initiated too late in pregnancy in these trials.

Growing points

A small number of studies have shown inconsistent associations of maternal thyroid dysfunction with offspring cardiometabolic indices including blood pressure and body weight. Correction of maternal thyroid dysfunction was, however, associated with favourable long-term metabolic profiles in mothers, including lipid profiles, fat mass and body mass index. Antenatal thyroid screening may therefore present opportunities for optimizing a wider range of outcomes than envisaged.

Areas for developing research

Future trials with early antenatal thyroid screening and intervention are necessary to clarify the impact of screening on late offspring and maternal effects.
Ligand-free mitochondria-localized mutant AR-induced cytotoxicity in spinal bulbar muscular atrophy
Authors: Feng Xia , Cheng Xiu-Tang , Zheng Pengli , Li Yan , Hakim Jill , Zhang Shirley Q , Anderson Stacie M , Linask Kaari , Prestil Ryan , Zou Jizhong , Sheng Zu-Hang , Blackstone Craig
Published: July 2022

Spinal bulbar muscular atrophy (SBMA), the first identified CAG-repeat expansion disorder, is an X-linked neuromuscular disorder involving CAG-repeat-expansion mutations in the androgen receptor (AR) gene. We utilized CRISPR-Cas9 gene editing to engineer novel isogenic human induced pluripotent stem cell (hiPSC) models, consisting of isogenic AR knockout, control and disease lines expressing mutant AR with distinct repeat lengths, as well as control and disease lines expressing FLAG-tagged wild-type and mutant AR, respectively. Adapting a small-molecule cocktail-directed approach, we differentiate the isogenic hiPSC models into motor neuron-like cells with a highly enriched population to uncover cell-type-specific mechanisms underlying SBMA and to distinguish gain- from loss-of-function properties of mutant AR in disease motor neurons. We demonstrate that ligand-free mutant AR causes drastic mitochondrial dysfunction in neurites of differentiated disease motor neurons due to gain-of-function mechanisms and such cytotoxicity can be amplified upon ligand (androgens) treatment. We further show that aberrant interaction between ligand-free, mitochondria-localized mutant AR and F-ATP synthase is associated with compromised mitochondrial respiration and multiple other mitochondrial impairments. These findings counter the established notion that androgens are requisite for mutant AR-induced cytotoxicity in SBMA, reveal a compelling mechanistic link between ligand-free mutant AR, F-ATP synthase and mitochondrial dysfunction, and provide innovative insights into motor neuron-specific therapeutic interventions for SBMA.
Your brain is amazing: Let’s keep it that way
Authors: Spires-Jones Tara L
Published: July 2022

Our editor discusses brain resilience and how it can be harnessed to prevent diseases that cause dementia.
Disentangling dyskinesia from parkinsonism in motor structures of patients with schizophrenia
Authors: Sakreida Katrin , Chiu Wei-Hua , Dukart Juergen , Eickhoff Simon B , Frodl Thomas , Gaser Christian , Landgrebe Michael , Langguth Berthold , Mirlach Daniela , Rautu Ioana-Sabina , Wittmann Markus , Poeppl Timm B
Published: July 2022

Patients with schizophrenia frequently suffer from motor abnormalities, but underlying alterations in neuroarchitecture remain unclear. Here, we aimed to disentangle dyskinesia from parkinsonism in motor structures of patients with schizophrenia and to assess associated molecular architecture. We measured grey matter of motor regions and correlated volumetric estimates with dyskinesia and parkinsonism severity. Associations with molecular architecture were identified by cross-modal spatial correlations between ensuing maps of abnormality-related volume alterations and neurotransmitter maps from healthy populations. Both phenomena were linked to (specific) striatal and basal forebrain reductions as well as to D1 receptor density. Dyskinesia also manifested in cerebellar decrease, while parkinsonism was associated with less motor cortex volume. The parkinsonism-related brain pattern was additionally associated with 5-HT1A/2A and µ-opioid receptors distribution. Findings suggest the need to develop psychopharmacological compounds that display not only selectivity for receptor subtypes but also anatomical selectivity for alleviating dyskinesia without worsening parkinsonism and vice versa.
Intratumoral microbiota: new frontiers in tumor immunity
Authors: Zhang Zhilin , Liao Yiqun , Tang Dong
Published: July 2022

Microbiota–host interactions are a hot topic of research because of their important role in regulating the malignant transformation of cancer cells and cancer-related immunity. The role of gut microbiota, oral microbiota and skin microbiota in cancer progression has been extensively studied. However, intratumoral microbiota is a recently discovered topic of research that is still in its infancy. This review focuses on the impact of the intratumoral microbiota on cancer immune responses and highlights how the intratumoral microbiota modulates innate and adaptive immunity to potentially impact tumor immunotherapy in the hope that it will inspire potential ideas for the application of immunotherapy in the treatment of tumors.
Sustained Within-season Vaccine Effectiveness Against Influenza-associated Hospitalization in Children: Evidence From the New Vaccine Surveillance Network, 2015–2016 Through 2019–2020
Authors: Sahni Leila C , Naioti Eric A , Olson Samantha M , Campbell Angela P , Michaels Marian G , Williams John V , Staat Mary Allen , Schlaudecker Elizabeth P , McNeal Monica M , Halasa Natasha B , Stewart Laura S , Chappell James D , Englund Janet A , Klein Eileen J , Szilagyi Peter G , Weinberg Geoffrey A , Harrison Christopher J , Selvarangan Rangaraj , Schuster Jennifer E , Azimi Parvin H , Singer Monica N , Avadhanula Vasanthi , Piedra Pedro A , Munoz Flor M , Patel Manish M , Boom Julie A
Published: July 2022

Background

Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.

Methods

We conducted a prospective, test-negative study of children 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015–2016 through 2019–2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% × (1 – odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.

Results

Of 8430 children, 4653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs 57%, P < .001); overall VE against hospitalization was 53% (95% confidence interval [CI]: 46, 60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (−3.2%, 12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4000, P = .275). Odds of hospitalization increased 2.9% (95% CI: −5.4%, 11.8%) and 9.6% (95% CI: −7.0%, 29.1%) per month in children ≤8 years (n = 3084) and 9–17 years (n = 916), respectively. These findings were not statistically significant.

Conclusions

We observed minimal, not statistically significant within-season declines in VE. Vaccination following current Advisory Committee on Immunization Practices (ACIP) guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.
Sotrovimab Resistance and Viral Persistence After Treatment of Immunocompromised Patients Infected With the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant
Authors: Huygens Sammy , Oude Munnink Bas , Gharbharan Arvind , Koopmans Marion , Rijnders Bart
Published: July 2022

Viral evolution was evaluated in 47 immunocompromised patients treated with sotrovimab. Sequencing of SARS-CoV-2 following therapy was successful in 16. Mutations associated with sotrovimab resistance were documented in 6; viral replication continued after 30 days in 5. Combination antibody therapy may be required to avoid acquired resistance in immunocompromised patients.
Guideline-Concordant Antiviral Treatment in Children at High Risk for Influenza Complications
Authors: Antoon James W , Hall Matt , Feinstein James A , Kyler Kathryn E , Shah Samir S , Girdwood Sonya Tang , Goldman Jennifer L , Grijalva Carlos G , Williams Derek J
Published: July 2022

Background

National guidelines recommend antiviral treatment for children with influenza at high risk for complications regardless of symptom duration. Little is known about concordance of clinical practice with this recommendation.

Methods

We performed a cross-sectional study of outpatient children (aged 1–18 years) at high risk for complications who were diagnosed with influenza during the 2016–2019 influenza seasons. High-risk status was determined using an existing definition that includes age, comorbidities, and residence in a long-term care facility. The primary outcome was influenza antiviral dispensing within 2 days of influenza diagnosis. We determined patient- and provider-level factors associated with guideline-concordant treatment using multivariable logistic regression.

Results

Of the 274 213 children with influenza at high risk for influenza complications, 159 350 (58.1%) received antiviral treatment. Antiviral treatment was associated with the presence of asthma (aOR, 1.13; 95% confidence interval [CI], 1.11–1.16), immunosuppression (aOR, 1.10; 95% CI, 1.05–1.16), complex chronic conditions (aOR, 1.04; 95% CI, 1.01–1.07), and index encounter in the urgent care setting (aOR, 1.3; 95% CI, 1.26–1.34). Factors associated with decreased odds of antiviral treatment include age 2–5 years compared with 6–17 years (aOR, 0.95; 95% CI, .93–.97), residing in a chronic care facility (aOR, .61; 95% CI, .46–.81), and index encounter in an emergency department (aOR, 0.66; 95% CI, .63–.71).

Conclusions

Among children with influenza at high risk for complications, 42% did not receive guideline-concordant antiviral treatment. Further study is needed to elucidate barriers to appropriate use of antivirals in this vulnerable population.
Coping with drought? Effects of extended drought conditions on soil invertebrate prey and diet selection by a fossorial amphisbaenian reptile
Authors: Martín José , Ortega Jesús , García-Roa Roberto , Rodríguez-Ruiz Gonzalo , Pérez-Cembranos Ana , Pérez-Mellado Valentín
Published: July 2022

Arid climates are characterized by a summer drought period to which animals seem adapted. However, in some years, the drought can extend for unusually longer periods. Examining the effects of these current extreme weather events on biodiversity can help to understand the effects of climate change, as models predict an increase in drought severity. Here, we examined the effects of “unusual” extended drought on soil invertebrate prey availability and on diet composition (based on fecal contents) and diet selection of a fossorial amphisbaenian, the checkerboard worm lizard Trogonophis wiegmanni. Weather data show interannual variations in summer drought duration. The abundance and diversity of soil invertebrates in spring were high, and similar to those found in a “normal” early autumn, after some rain had ended with the summer drought. In contrast, in years with “unusual” extended drought, abundance, and diversity of soil invertebrates in early autumn were very low. Also, there were seasonal changes in amphisbaenians’ diet; in autumn with drought, prey diversity, and niche breadth decreased with respect to spring and autumns after some rain had fallen. Amphisbaenians did not eat prey at random in any season, but made some changes in prey selection that may result from drought-related restrictions in prey availability. Finally, in spite that amphisbaenians showed some feeding flexibility, their body condition was lower in autumn than in spring, and much lower in autumn with drought. If extended drought became the norm in the future, amphisbaenians might suffer important negative effects for their health state.
Echo-Doppler and strain assessment of filling pressures in adults with congenitally corrected transposition and systemic right ventricles
Authors: Charles Jain C , Egbe Alexander C , Oh Jae K , Connolly Heidi M , Miranda William R
Published: July 2022

Aims

Systolic dysfunction of the systemic right ventricle (sRV) is common in adults with transposition of the great arteries and sRV. In acquired disease, diastology analysis for assessment of filling pressures (FP) is paramount in patient care.

Methods and results

Retrospective analysis of 47 adults with sRV without prior systemic tricuspid valve surgery undergoing catheterization and echocardiography within 7 days (median −2 [−1, −3]) from January 2000 to February 2021 at our institution. Median age was 48 (31, 55) years, and 16 (34.0%) patients were female. FPs were normal in 21 patients (44.7%). Left atrial size was enlarged in most patients (83.0%) with mean indexed value 58.3 ± 23.4 mL/m2. Tissue Doppler e′ was not significantly different between those with high FPs vs. normal (medial 0.07 ± 0.03 vs. 0.08 ± 0.03 m/s, P = 0.63; lateral 0.08 ± 0.04 vs. 0.08 ± 0.04 m/s, P = 0.88). E velocity and subpulmonic mitral regurgitant velocity were higher in those with high FPs (0.9 ± 0.3 vs. 0.6 ± 0.2 m/s, P = 0.005; 3.8 ± 1.1 vs. 2.8 ± 0.9 m/s, P = 0.004). Left atrial reservoir strain, sRV global longitudinal strain, and subpulmonic left ventricular strain were worse in those with high FP (18.0 ± 7.6 vs. 27.9 ± 10.2%, P = 0.0009; −13.0 ± 4.4 vs. −17.9 ± 5.0%, P = 0.002; −16.8 ± 5.7 vs. −23.0 ± 3.8%, P = 0.001).

Conclusion

Despite the complex anatomy, FPs can be assessed non-invasively in adults with sRV without prior systemic tricuspid valve surgery. The current guideline algorithm for diastolic dysfunction in acquired heart disease has limited applicability in this population. Given the limitations of Doppler in this heterogeneous population, strain analysis can be a helpful adjunct for estimation of FPs.
Extrapulmonary sarcoidosis involving only the heart and guts: a case report
Authors: Sasaki Shun , Hayashi Takaharu , Tateishi Emi , Higuchi Yoshiharu
Published: July 2022

Background

The respiratory tract is the most commonly affected organ system in sarcoidosis. Purely extrapulmonary sarcoidosis is rare. There have been no reports of extrapulmonary sarcoidosis with lesions only in the heart and guts.

Case summary

A 19-year-old male was admitted for chest symptoms accompanied by remarkably elevated troponin T and creatinine kinase levels. Electrocardiogram (ECG) showed sinus rhythm with a right bundle branch block, broad ST segment elevation, and abnormal Q waves. Endoscopic biopsy revealed granuloma formation in the transverse colon. Based on multimodal imaging, we made a clinical diagnosis of extrapulmonary sarcoidosis involving only the heart and guts. One year of immunosuppressive therapy with prednisolone resolved the inflammation in the guts but not in the heart. He experienced runs of sustained ventricular tachycardia with loss of consciousness and was admitted to our hospital again. The addition of methotrexate markedly reduced cardiac accumulation of fluorodeoxyglucose. No life-threatening ventricular arrhythmias have been recorded afterwards.

Discussion

This unusual case of cardiac sarcoidosis not only involved rare lesions only in the heart and guts but also presented with ST elevation on ECG. This case suggests that the gastrointestinal tract is a site of effective antigen capture outside of the respiratory tract that can affect the heart.
The impact of the rice production system (irrigated vs lowland) on root-associated microbiome from farmer's fields in western Burkina Faso
Authors: Barro Mariam , Wonni Issa , Simonin Marie , Kassankogno Abalo Itolou , Klonowska Agnieszka , Moulin Lionel , Béna Gilles , Somda Irénée , Brunel Caroline , Tollenaere Charlotte
Published: July 2022

Due to their potential applications for food safety, there is a growing interest in rice root-associated microbial communities, but some systems remain understudied. Here, we compare the assemblage of root-associated microbiota in rice sampled in 19 small farmer's fields from irrigated and rainfed lowlands in Burkina Faso, using an amplicon metabarcoding approach of the 16S rRNA gene (prokaryotes, three plant samples per field) and ITS (fungi, one sample per field). In addition to the expected structure by root compartments (root vs rhizosphere) and geographical zones, we showed that the rice production system is a major driver of microbiome structure. In irrigated systems, we found a higher diversity of prokaryotic communities from the rhizosphere and more complex co-occurrence networks, compared to rainfed lowlands, while fungal communities exhibited an opposite pattern (higher richness in rainfed lowlands). Core taxa were different between the two systems, and indicator species were identified: mostly within Bacillaceae in rainfed lowlands, and within Burkholderiaceae and Moraxellaceae in irrigated areas. Finally, a higher abundance in rainfed lowlands was found for mycorrhizal fungi (both compartments) and rhizobia (rhizosphere only). Our results highlight deep microbiome differences induced by contrasted rice production systems that should consequently be considered for microbial engineering applications.
United States Family Forest Owners’ Awareness of and Participation in Carbon Sequestration Programs: Initial Findings from the USDA Forest Service National Woodland Owner Survey
Authors: Sass Emma M , Caputo Jesse , Butler Brett J
Published: July 2022

Family forest owners (FFOs) hold a plurality of forestland in the United States, and programs and markets exist that compensate landowners for sequestering and storing increased carbon through extended rotations, improved forest management, and increased forest cover. We used USDA Forest Service National Woodland Owner Survey (NWOS) data from 2018 to estimate the number of ownerships and their associated acreage that are enrolled, that are familiar but not enrolled, and that are unfamiliar with these programs, as well as differences in attributes among these groups. As of 2018, less than 0.1% (SE < 0.1%) of FFOs are enrolled in carbon sequestration programs, and collectively they hold an estimated 400,000 ha (SE = 100,000). FFOs who are enrolled have larger holdings, are more likely to participate in other programs, and are more concerned about climate change, among other characteristics. Most FFO holdings are too small to be viable in traditional carbon programs, although new and evolving programs might enable smaller landholdings to be feasible to enroll. Knowing the characteristics of ownerships that are enrolled or aware of programs will allow for more informed design and implementation; future monitoring will be important to identify trends as these programs become more widespread.
Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis
Authors: Momen Mehdi , Brounts Sabrina H , Binversie Emily E , Sample Susannah J , Rosa Guilherme J M , Davis Brian W , Muir Peter
Published: July 2022

Degenerative suspensory ligament desmitis is a progressive idiopathic condition that leads to scarring and rupture of suspensory ligament fibers in multiple limbs in horses. The prevalence of degenerative suspensory ligament desmitis is breed related. Risk is high in the Peruvian Horse, whereas pony and draft breeds have low breed risk. Degenerative suspensory ligament desmitis occurs in families of Peruvian Horses, but its genetic architecture has not been definitively determined. We investigated contrasts between breeds with differing risk of degenerative suspensory ligament desmitis and identified associated risk variants and candidate genes. We analyzed 670k single nucleotide polymorphisms from 10 breeds, each of which was assigned one of the four breed degenerative suspensory ligament desmitis risk categories: control (Belgian, Icelandic Horse, Shetland Pony, and Welsh Pony), low risk (Lusitano, Arabian), medium risk (Standardbred, Thoroughbred, Quarter Horse), and high risk (Peruvian Horse). Single nucleotide polymorphisms were used for genome-wide association and selection signature analysis using breed-assigned risk levels. We found that the Peruvian Horse is a population with low effective population size and our breed contrasts suggest that degenerative suspensory ligament desmitis is a polygenic disease. Variant frequency exhibited signatures of positive selection across degenerative suspensory ligament desmitis breed risk groups on chromosomes 7, 18, and 23. Our results suggest degenerative suspensory ligament desmitis breed risk is associated with disturbances to suspensory ligament homeostasis where matrix responses to mechanical loading are perturbed through disturbances to aging in tendon (PIN1), mechanotransduction (KANK1, KANK2, JUNB, SEMA7A), collagen synthesis (COL4A1, COL5A2, COL5A3, COL6A5), matrix responses to hypoxia (PRDX2), lipid metabolism (LDLR, VLDLR), and BMP signaling (GREM2). Our results do not suggest that suspensory ligament proteoglycan turnover is a primary factor in disease pathogenesis.
Diminished Tubule Epithelial Farnesoid X Receptor Expression Exacerbates Inflammation and Fibrosis Response in Aged Rat Kidney
Authors: Ha Sugyeong , Yang Yejin , Won Kim Jeong , Son Minjung , Kim Doyeon , Kim Mi-Jeong , Im Dong-Soon , Young Chung Hae , Chung Ki Wung
Published: July 2022

The age-associated functional decline of the kidney is accompanied by structural changes including glomerular sclerosis and interstitial fibrosis. Aging kidneys also exhibit increased vulnerability in stressful environmental conditions. In this study, we assessed the differences in responses between young and aged animals to folic acid (FA)-induced renal fibrosis. To monitor the effects of aging on FA-induced kidney fibrosis, we administered FA (250 mg/kg) to young (6-month old) and aged (20-month old) rats. The development of severe fibrosis was only detected in aged rat kidneys, which was accompanied by increased kidney injury and inflammation. Furthermore, we found that FA-treated aged rats had significantly lower farnesoid X receptor (FXR) expression in the tubular epithelial cells than the rats not treated with FA. Interestingly, the extent of inflammation was severe in the kidneys of aged rat, where the FXR expression was low. To explore the role of FXR in kidney inflammation, in vitro studies were performed using NRK52E kidney tubule epithelial cells. NF-κB activation by lipopolysaccharide treatment induces chemokine production in NRK52E cells. The activation of FXR by obeticholic acid significantly reduced the transcriptional activity of NF-κB and chemokine production. In contrast, FXR knockdown increased LPS-induced chemokine production in NRK52E cells. Finally, FXR-knockout mice that were administered FA showed increased inflammation and severe fibrosis. In summary, we demonstrated that diminished FXR expression in the epithelial cells of the renal tubules exacerbated the fibrotic response in aged rat kidneys by upregulating pro-inflammatory NF-κB activation.
Is Transition in Living Arrangements Associated With Older Adults’ Life Satisfaction When Preference Is Considered?
Authors: Sun Rongjun , Zimmer Zachary
Published: July 2022

Objectives

In a longitudinal design, the objective is to investigate the association between transitions in living arrangements and life satisfaction with special consideration for preferred living arrangement, and to assess whether such associations are moderated by age among Chinese older adults.

Methods

Data were from 4 waves of the Chinese Longitudinal Healthy Longevity Survey, 2005–2014. Living arrangement transitions (N = 12,654) distinguished coresidence with children and non-coresidence and matched preference. Random effect ordinal logistic models predicted life satisfaction by transitions in living arrangements between baseline and follow-up, transitions in matched living arrangement preferences between baseline and follow-up, and these transitions interacted with age at baseline, adjusting for life satisfaction at baseline. Predicted probabilities for the highest level of life satisfaction for several transition combinations were calculated and the difference was tested for significance.

Results

Although matching actual and preferred living arrangement transition is an important factor in determining life satisfaction, actual coresidence with children remains positively significant. Moreover, results show significant interaction effects of the two transitions with age: while the association of life satisfaction with consistent matching gradually declines into older ages, the association of life satisfaction with consistent coresidence increases with age.

Discussion

While preference-matched living arrangement is critical for life satisfaction, especially for the young-old, the role of coresidence becomes more prominent at very old ages when various needs are likely to arise. It is too early to dismiss the role of coresidence with children in the Chinese context.
Spherical Monadic Adjunctions of Stable Infinity Categories
Authors: Christ Merlin
Published: July 2022

This paper concerns spherical adjunctions of stable $\infty $-categories and their relation to monadic adjunctions. We begin with a proof of the 2/4 property of spherical adjunctions in the setting of stable $\infty $-categories. The proof is based on the description of spherical adjunctions as $4$-periodic semiorthogonal decompositions given by Halpern-Leistner and Shipman [4] and Dyckerhoff et al. [3]. We then describe a class of examples of spherical adjunctions arising from local systems on spheres. The main result of this paper is a characterization of the sphericalness of a monadic adjunctions in terms of properties of the monad. Namely, a monadic adjunction is spherical if and only if the twist functor is an equivalence and commutes with the unit map of the monad. This characterization is inspired by work of Segal [10].
Hilbert’s Irreducibility Theorem via Random Walks
Authors: Bary-Soroker Lior , Garzoni Daniele
Published: July 2022

Let $G$ be a connected linear algebraic group over a number field $K$, let $\Gamma $ be a finitely generated Zariski dense subgroup of $G(K)$, and let $Z\subseteq G(K)$ be a thin set, in the sense of Serre. We prove that, if $G/\textrm {R}_{u}(G)$ is either trivial or semisimple and $Z$ satisfies certain necessary conditions, then a long random walk on a Cayley graph of $\Gamma $ hits elements of $Z$ with negligible probability. We deduce corollaries to Galois covers, characteristic polynomials, and fixed points in group actions. We also prove analogous results in the case where $K$ is a global function field.
Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa
Authors: Ramassamy Jill-Léa , Bilounga Ndongo Chanceline , Nnuka Patrick , Antunes Maëlle , Le Mener Margot , Betsem a Betsem Edouard , Njouom Richard , Cassar Olivier , Fontanet Arnaud , Gessain Antoine
Published: July 2022

Background

Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon.

Methods

From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses.

Results

Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7–1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3–6.2), history of surgery (aOR, 6.3; 95% CI, 2.2–17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2–19.8).

Conclusions

These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.
PRO: Biomarker surveillance for invasive fungal infections without antifungal prophylaxis could safely reduce antifungal use in acute leukaemia
Authors: Taynton Thomas , Barlow Gavin , Allsup David
Published: July 2022

Mould-active antifungal prophylaxis is frequently used to prevent invasive fungal infection in patients with acute leukaemia being treated with intensive chemotherapy. Invasive fungal infections are difficult to diagnose, and despite the use of prophylaxis a high proportion of patients still receive therapeutic antifungals. Antifungal medications have important interactions, can cause serious adverse events, and may drive the proliferation of antifungal resistance. The use of two biomarkers, such as galactomannan in combination with the less-specific β-d-glucan, can mitigate the risk of not detecting non-Aspergillus species, as well as improving pooled sensitivity and specificity. We argue that regular biomarkers could be used safely as part of an antifungal stewardship strategy to reduce antifungal use, by both screening for infection in patients not on prophylaxis and ruling out infection in patients treated empirically.
Should serum biomarker monitoring replace primary antifungal chemoprophylaxis in patients with acute leukaemia receiving systemic anti-cancer therapy? A PRO/CON debate
Authors: Harrison Thomas , Partridge David
Published: July 2022

Fungal infection exacts a severe burden on patients with acute leukaemia. Azole prophylaxis attempts to mitigate this impact but is associated with toxicity and cost as well as the potential to select for resistance. The development of biomarkers including galactomannan and β-1,3-d-glucan may improve detection of early disease and thus reduce the need for prophylaxis, though these assays also have their limitations. In this debate, Howard et al. argue in favour of continuing chemoprophylaxis in patients with acute leukaemia receiving systemic chemotherapy, citing the multiple randomized control trials and meta-analyses that demonstrate its efficacy. Taynton et al. argue that fungal biomarker surveillance in the absence of primary antifungal chemoprophylaxis is a safe alternative that could reduce antifungal use and the development of resistance.
Origin versus Substance: Competing Determinants of Disruption in Duplication Technologies
Authors: Zheng Yanmei , Alba Joseph W
Published: July 2022

Contemporary developments in material duplication promise product alternatives that are physically and sensorially indistinguishable from incumbent offerings. When fully realized, such duplicate offerings should obsolete the incumbents as a consequence of wider availability and lower monetary and social costs. Disruption will be impeded, however, if consumers favor incumbent products on the basis of non-material qualities. The authors show that the influence of such qualities depends on both the product category and characteristics of the consumer. In particular, when a creator is central to the product and when the consumer is inclined toward extraordinary beliefs, the influence of origin looms especially large. By contrasting origin and substance, the present research exposes dualistic thinking in consumers’ product evaluations, enriches prior research on authenticity and extraordinary beliefs, and contributes to the stubborn problem of technology adoption.
Trends in Bark Beetle Impacts in North America During a Period (2000–2020) of Rapid Environmental Change
Authors: Fettig Christopher J , Asaro Christopher , Nowak John T , Dodds Kevin J , Gandhi Kamal J K , Moan Jason E , Robert Jeanne
Published: July 2022

Of the more than five hundred and fifty species of North American bark beetles (Coleoptera: Curculionidae, Scolytinae), approximately twenty species occasionally cause large amounts of tree mortality in conifer forests. During 2000–2020, trends in bark beetle impacts changed dramatically across North America compared to those observed during the mid- to late 20th century. We review tools and tactics available for bark beetle suppression and prevention and provide an overview of temporal and spatial trends in bark beetle impacts in North American forests during 2000–2020. Higher impacts were observed for several bark beetle species in western North America accompanied by substantial declines in eastern North America driven by large reductions in southern pine beetle (Dendroctonus frontalis) activity in the southeastern United States. Regional differences likely result from a higher species richness of both bark beetles and their hosts in western North America, stronger direct and indirect effects of climate change (warming and drying) on bark beetles in western North America, and differences in forest composition, management history, and other abiotic stressors and disturbances.

Study Implications

Compared to the mid- to late 20th century, bark beetles have had increased impacts in western North America and reduced impacts in eastern North America, the latter driven by large reductions in southern pine beetle (Dendroctonus frontalis) activity in the southeastern United States. We review tools and tactics available to foresters and other natural resource managers to reduce the negative impacts of bark beetles on forests. Furthermore, we provide several potential explanations for recent trends in bark beetle impacts between eastern and western North America.
A comprehensive review of phytochemistry, pharmacology and quality control of plants from the genus Viola
Authors: Zhang Qing , Wang Qing , Chen Suiqing
Published: July 2022

Objectives

The genus Viola belongs to the family Violaceae, and the plants from this genus are essential folk herb medicine extensively used in many areas. The plants from the genus Viola are used to treat various diseases and exert a significant role in protecting people’s health. This review summarized the genus Viola plants’ phytochemistry, pharmacology, and quality control methods.

Key findings

The information on chemical constituents and pharmacological effects of the genus Viola was obtained by searching the Web of Science, Pubmed, CNKI, and other databases. A total of 208 valuable articles were selected and analyzed in this review. The main chemical components of plants from the genus Viola consist of flavonoids, coumarins, alkaloids, lignans, sesquiterpenes, cyclotides, etc. The active chemical components of medicinal plants from this genus exert antibacterial, antiviral, antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective activities, and so on. The quality control of these plants is not sufficient and needs further research.

The chemical constituents, pharmacological effects, and quality control of plants from the genus Viola were systematically summarized in this paper, and this review provides a literature basis for the further research of plants from this genus.
Up-regulation of bZIP88 transcription factor is involved in resistance to three different herbicides in both Echinochloa crus-galli and E. glabrescens
Authors: Zhang Yuhua , Gao Haitao , Fang Jiapeng , Wang Hao , Chen Jinyi , Li Jun , Dong Liyao
Published: July 2022

The resistance of weeds to herbicides poses a major threat to agricultural production, and non-target-site resistance (NTSR) is often a serious problem as its mechanisms can in some cases confer resistance to herbicides with different modes of action. In this study, we hypothesized that bZIP transcription factors (TFs), which regulate abiotic stress responses in many plants, play a regulatory role in NTSR. Whole-plant assays indicated that the wild grasses Echinochloa crus-galli and E. glabrescens are resistant to the herbicides penoxsulam, cyhalofop-butyl, and quintrione. Transcriptome sequencing then identified 101 and 49 bZIP TFs with differential expression following penoxsulam treatment in E. crus-galli and E. glabrescens, respectively. Twelve of these genes had >60% homology with rice genes. The expression of bZIP88 was considerably up-regulated 6 h after treatment with the three different herbicides, and it was similar between resistant and susceptible populations; however, the relative expression levels before herbicide treatment and 24 h after were the same. We used rice (Oryza sativa ssp. japonica cv Nipponbare) as a model system for functional validation and found that CRISPR-Cas9-knockout of the rice bZIP88 ortholog increased the sensitivity to herbicide, whereas overexpression reduced it. The OsbZIP88 protein was localized to the nucleus. Using ChIP coupled with high-throughput sequencing, OsbZIP88 was found to form a network regulatory center with other TFs such as bZIP20/52/59 to regulate OsKS1, OsCOE1, and OsIM1, which are related to auxin, abscisic acid, brassinosteroids, and gibberellic acid. Based on these results, we have established a database of bZIP TFs corresponding to herbicide stress, and resolved the mechanisms of the positive regulation of herbicide resistance by bZIP88, thereby providing new insights for NTSR.
The Schlemiel and the Messianic in Michael Chabon’sThe Yiddish Policemen’s Unionand Nicole Krauss’sForest Dark
Authors: Sabbath Roberta
Published: July 2022

The Jewish diaspora of the United States views the historical sequence of Holocaust, known more accurately as the Shoah, and creation of the State of Israel as connected in an apocalyptic-redemptive narrative typology. The Nazi regime murdered six million Jews, including one and one-half million children, based on racial hatred and seven million others deemed undesirable. In 1949, four years after the defeat of the Nazi regime and liberation from the camps, the State of Israel was admitted into the United Nations as its 59th member. The belief in messianic redemption during times of great suffering has been a part of Jewish history for millennia. The first important surviving manuscripts expressing messianic beliefs are the Dead Sea Scrolls (300-100 BCE). The Book of Daniel (200 BCE) predicts the coming of a Son of Man. Jewish messianic beliefs suggest that the messiah is an earthly human being who will change earthly history. However, core Jewish writings through the centuries resist messianic movements and messianic dreams. This latter tradition of resistance shows up as a critique of the messianic typology of Holocaust-to-State of Israel in two works of contemporary authors, Michael Chabon’s The Yiddish Policeman’s Union (2007) and Nicole Krauss’s Forest Dark (2017). At the same time, Chabon and Krauss maintain a strong Jewish self-identity and recognize continuing hatred by white supremacists and other global anti-Semitic movements. The resulting novels use parody as a form of gentle critique, Chabon with a story of alternate history and Krauss with a braided strategy of parallel narratives.
Aspergillusspp. osteoarticular infections: an updated systematic review on the diagnosis, treatment and outcomes of 186 confirmed cases
Authors: Tsantes Andreas G , Papadopoulos Dimitrios V , Markou Eleftheria , Zarokostas Konstantinos , Sokou Rozeta , Trikoupis Ioannis , Mavrogenis Andreas F , Houhoula Dimitra , Piovani Daniele , Bonovas Stefanos , Tsantes Argirios E , Tsakris Athanasios , Vrioni Georgia
Published: July 2022

Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is to investigate the current literature regarding Aspergillus spp. osteoarticular infections. An electronic search of the PubMed and Scopus databases was conducted considering studies that assessed osteoarticular infections from Aspergillus spp. We included only studies with biopsy proven documentation of positive cultures or histological findings for Aspergillus spp., and those with essential information for each case such as the anatomical location of the infection, the type of treatment (conservative, surgical, combination), the antifungal therapy, and the outcome. Overall, 148 studies from 1965 to 2021 including 186 patients were included in the review. One hundred and seven (57.5%) patients underwent surgical debridement in addition to antifungal therapy, while 79 (42.7%) patients were treated only conservatively. Complete infection resolution was reported in 107 (57.5%) patients, while partial resolution in 29 (15.5%) patients. Surgical debridement resulted in higher complete infection resolution rate compared to only antifungal therapy (70.0% vs. 40.5%, P < 0.001), while complete resolution rate was similar for antifungal monotherapy and combination/sequential therapy (58.3% vs. 54.5%; P = 0.76). Last, complete resolution rate was also similar for monotherapy with amphotericin B (58.1%) and voriconazole (58.6%; P = 0.95). The results of this study indicate that antifungal monotherapy has similar efficacy with combination/sequential therapy, while voriconazole has similar efficacy with amphotericin B. Moreover, surgical debridement of the infected focus results in better outcomes in terms of infection eradication compared to conservative treatment.

Lay Summary

Antifungal monotherapy has similar efficacy with combination/sequential therapy, and voriconazole has similar efficacy with amphotericin B for the treatment of Aspergillus spp. osteoarticular infections, while surgical debridement of the infected focus improves the infection eradication rate.
AA amyloidosis associated with cancers
Authors: Bharati Joyita , Lahoud Oscar B , Jhaveri Kenar D , Izzedine Hassan
Published: July 2022

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.
Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis
Authors: Oberkampf Florence , Gutierrez Maya , Trabelsi Grati Olfa , Le Rhun Émilie , Trédan Olivier , Turbiez Isabelle , Kadi Amir , Dubot Coraline , Taillibert Sophie , Vacher Sophie , Bonneau Claire
Published: July 2022

Background

Patients with HER2-positive breast cancer (HER2 + BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer. Leptomeningeal progression results in a drastically altered prognosis with limited therapeutic options. This phase II study was conducted to assess the efficacy of intrathecal (IT) trastuzumab in HER2 + BC patients with leptomeningeal metastasis (LM), based on a phase I dose-escalation study that had determined the recommended weekly dose of 150 mg for phase II.

Methods

Eligible patients received weekly administrations of 150 mg of IT trastuzumab. The primary endpoint was clinical neurologic progression-free survival (LM-related-PFS) after 8 weeks. Overall survival (OS), toxicities, and quality of life (QoL) were secondary endpoints.

Results

Among the 19 enrolled patients, 16 (84%) had concomitant brain metastases, 15 of them had received prior radiotherapy to the brain. All patients had received at least one line of systemic anti-HER2 therapy. After 8 weeks, 14 patients (74%) were free of neurological progression. The median LM-related-PFS was 5.9 months and the median OS was 7.9 months. According to the QLQ-C30 and BN20 scales, the global health-related QoL status seemed preserved and no toxicity above grade 3 was observed.

Conclusions

Conducting studies on patients with LM poses significant challenges and ethical dilemmas inherent to this population. Despite some limits, this phase II study’s findings in terms of clinical neurologic response and QoL’s control confirms weekly administration of 150 mg of IT trastuzumab as a valuable option for HER + BC patients with LM and support the interest for further investigations.