bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the clinical and mechanistic effects of eplerenone and amiloride monotherapy, and combination therapy with cinacalcet, in primary hyperparathyroidism: A placebo‐controlled randomized trial
Authors: Parksook Wasita W. , Heydarpour Mahyar , Brown Jenifer M. , Turchin Alexander , Mannstadt Michael , Vaidya Anand
Published: November 2022

Objectives

Human physiology and epidemiology studies have demonstrated complex interactions between the renin–angiotensin–aldosterone system, parathyroid hormone and calcium homeostasis. Several of these studies have suggested that aldosterone inhibition may lower parathyroid hormone (PTH) levels. The objective of this study was to assess the effect of 4 weeks of maximally tolerated mineralocorticoid receptor antagonist therapy with eplerenone on PTH levels in patients with primary hyperparathyroidism (P‐HPT) when compared to amiloride and placebo. We also investigated the synergistic effect of these interventions when combined with cinacalcet for an additional 2 weeks.

Design

Randomized, double‐blinded, three parallel‐group, placebo‐controlled trial.

Patients

Patients with P‐HPT.

Results

Most patients were women (83%) and White (76%). Maximally tolerated doses of eplerenone and amiloride induced significant reductions in blood pressure and increases in renin and aldosterone production; however, despite these physiologic changes, neither intervention induced significant changes in PTH or calcium levels when compared to the placebo. Both eplerenone and amiloride therapy induced significant reductions in procollagen type 1 N‐terminal propeptide levels when compared to placebo. When cinacalcet therapy was added, PTH and calcium levels were markedly reduced in all groups; however, there was no significant difference in PTH or serum calcium reductions between groups.

Conclusions

Although maximally tolerated therapy with eplerenone and amiloride induced expected changes in renin, aldosterone and blood pressure, there were no meaningful changes in PTH or serum calcium levels in P‐HPT patients. These results suggest that inhibition of aldosterone action does not have a clinically meaningful role in medical therapy for P‐HPT.
Wound healing in endoscopic sinus surgery: Phase 1 clinical trial evaluating the role of Chitogel with adjuvants
Authors: Vediappan Rajan Sundaresan , Bennett Catherine , Cooksley Clare , Bassiouni Ahmed , Scott John R. , Al Suliman Yazeed A. , Lumyongsatien Jate , Moratti Stephen , Psaltis Alkis J. , Vreugde Sarah , Wormald Peter‐John
Published: November 2022

Objectives

This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery.

Design

A double‐blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def‐GaPP versus no packing (control).

Setting

Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post‐operative (PO) dressings can improve PO wound healing and patient outcomes after ESS.

Participants

Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout.

Main Outcome Measures

Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT‐22, VAS and LKS, pre and post‐surgery (12 weeks) were compared.

Results

Seventy nine patients completed the study, there was a significant reduction in SNOT‐22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p < .05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no‐treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12‐week time point (p < .05).

Conclusion

Chitogel as a PO dressing after ESS results in the best patient‐reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.
Novel lncRNA‐prader willi/angelman region RNA, SNRPN neighbour (PWARSN) aggravates tubular epithelial cell pyroptosis by regulating TXNIP via dual way in diabetic kidney disease
Authors: Song Yi , Guo Feng , Zhao Yan‐yan , Ma Xiao‐jun , Wu Li‐na , Yu Ji‐feng , Ji Hong‐fei , Shao Ming‐wei , Huang Feng‐juan , Zhao Lin , Fan Xun‐jie , Xu Ya‐nan , Wang Qing‐zhu , Qin Gui‐jun
Published: November 2022

Objectives

Elevated thioredoxin‐interacting protein (TXNIP)‐induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear.

Materials and methods

Transcriptomic analysis identified a novel long noncoding RNA—Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)—which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP‐mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus‐mediated overexpression and CRISPR‐Cas9‐based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV‐9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced‐pyroptosis in DKD.

Results

TXNIP‐NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP‐driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR‐372‐3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X‐linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3‐enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD.

Conclusions

These findings illustrate distinct dual molecular mechanisms for PWARSN‐modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD.
Perceptions and uses of pangolins (Pholidota) among remote rural communities in the Republic of the Congo: A baseline study from the Odzala‐Kokoua National Park
Authors: Swiacká Markéta , Ingram Daniel J. , Bohm Torsten , Ceacero Francisco
Published: November 2022

Habitat loss and overexploitation are the most severe threats to wild animals in Central Africa. One mammalian group under pressure from hunting is the Pholidota (pangolins), with three species of pangolin inhabiting the region. While local uses of pangolins have been investigated in several Central African countries, data originating from the Republic of the Congo are lacking. To address this knowledge gap, we conducted a semistructured questionnaire survey in 65 rural communities around the Odzala‐Kokoua National Park. Our research focused on collecting baseline information on local knowledge of species ecology, and perceived economic values and uses of pangolins in local communities. We identified significant differences in our data corresponding to respondents' sociocultural and demographic profiles in the surveyed villages. Recognition of pangolins was high (98.2%), we recorded 22 traditional medicinal or cultural uses of pangolins by respondents, and the taste of pangolin meat was ranked highly (71.3%). Respondents based along the northern boundary of the park were more familiar with pangolins and the market value of their meat and scales, which could be due to better quality roads in the area and proximity to Cameroon. We then provide guidelines for further research to better understand the dynamics of local use, needed for conservation policy and actions.
Immune reconstitution and survival of patients after allogeneic hematopoietic stem cell transplantation from older donors
Authors: Jiang Peiyao , Cai Yu , Zhou Xiao , Yang Jun , Tong Yin , Huang Chongmei , Qiu Huiying , Zhou Kun , Xu Xiaowei , Zhang Ying , Niu Jiahua , Shen Chang , Xia Xinxin , Wei Yu , Song Xianmin , Wan Liping
Published: November 2022

Background

The impact of donor age on the immune reconstitution of patients with hematological malignancies who underwent hematopoietic cell transplantation (HCT) is unclear.

Method

We retrospectively compared the outcomes of 381 patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from 308 donors under 50 years of age and 73 donors over 50 years of age. IVIG was regularly supplemented for patients in the first 3 months post‐HCT.

Results

The counts of CD8+CD45RA+ naïve T cells were significantly lower in patients of the older donor group than in the younger donor group in the first year after PBSCT (190.6 cells/μl vs. 239.6 cells/μl, p = .018). Patients in the older donor group had significantly fewer CD19+ B cells on day +270 (123.4 cells/μl vs. 183.5 cells/μl, p = .021) and day +365 (169 cells/μl vs. 271.1 cells/μl, p = .01) after PBSCT. Serum IgA (.76 g/L vs. .97 g/L, p < .001) and IgM levels (.75 g/L vs. 1.04 g/L, p < .001) were significantly lower in patients in the older donor group from day +60 to +365 after PBSCT. The EBV reactivation rate within the first 3 months after PBSCT was significantly higher in patients in the older donor group (48.6% vs. 38.3%, p = .034). However, the incidences of CMV reactivation, II‐IV acute graft‐versus‐host disease (aGvHD), chronic GvHD (cGvHD), 3‐year relapse rate, 3‐year transplant‐related mortality (TRM) and 3‐year overall survival (OS) were not significantly different between the two groups.

Conclusion

In conclusion, donors ≥50 years old were associated with inferior immune reconstitution and higher EBV reactivation in patients after PBSCT, but no change in OS.
A test of the competitive ability–cold tolerance trade‐off hypothesis in seasonally breeding beetles
Authors: Wettlaufer Jillian D. , Ye April , MacMillan Heath A. , Martin Paul R.
Published: November 2022

Closely related species that use similar resources often differ in their seasonal patterns of activity, but the factors that limit their distributions across seasons are unknown for most species. One hypothesis to explain seasonal variation in the distributions of species involves a trade‐off between competitive ability and cold tolerance, where tolerance to the cold compromises competitive ability in warmer (benign) temperatures, either at the level of the individual or population.

We tested both individual‐level and population‐level mechanisms of this hypothesis in two co‐occurring species of temperate burying beetles (Silphidae: Nicrophorus sayi, N. orbicollis) that differ in their seasonal patterns of activity.

We measured cold tolerance, breeding activity as a function of temperature, and competitive ability as a function of temperature and season.

Consistent with our hypothesis, the mid‐season N. orbicollis was less able to function at the cold temperatures that characterise early spring, when the early‐season N. sayi is most active. The larger beetle, however, always won one‐on‐one competitive trials at warm temperatures, regardless of species, inconsistent with an individual‐level trade‐off. N. orbicollis was usually larger and successful when competing for the same carrion later in the season, mostly because of its larger population size, consistent with a trade‐off between competitive ability, and cold tolerance acting at the population level.

Our findings suggest that cold temperatures limit the mid‐season N. orbicollis from earlier spring emergence, while competitive pressure from the more abundant, larger N. orbicollis constrains the early‐season N. sayi from remaining active through the summer.
Aggregative oviposition varies with density in processionary moths—Implications for insect outbreak propensity
Authors: Battisti Andrea , Hódar José A. , Hernández Rodolfo , Larsson Stig
Published: November 2022

In gregarious insects, groups commonly originate from females laying eggs in masses and feeding groups are established as soon as larvae hatch. Some group‐living insect species may aggregate beyond the individual parent level, such that offspring from two or more egg masses develop within a common resource.

Here we show that aggregative oviposition can vary with population density at oviposition and possibly be an important factor in outbreak dynamics of phytophagous insects.

We analysed density data with respect to egg mass aggregation for two species of pine processionary moths,Thaumetopoea pinivora(in Sweden 2005–2019) andT. pityocampa(in Spain 1973–1991). Both species lay their eggs in egg masses and feed in groups. During the study periods, insect population density for both species varied by at least an order of magnitude.

The two species showed strikingly similar patterns of egg mass aggregation. Egg masses were overdispersed at high population density, with few trees showing a high load of egg masses.

Our data suggest that aggregative oviposition can be important in explaining the previously documented higher propensity for outbreaks in insects laying eggs in clusters, compared with those laying individual eggs.
Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex
Authors: Lynch Matthew , Smith Kirsty , Riney Kate
Published: November 2022

Objective

The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording.

Methods

Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video‐EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification.

Results

Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients.

Significance

This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.
The trend premium around the world: Evidence from the stock market
Authors: Lin Hai , Liu Pengfei , Zhang Cheng
Published: November 2022

This paper studies the predictive power of the trend strategy in the international stock market. Using data from 49 markets, we find that a trend signal exploiting the short‐, intermediate‐, and long‐term price information can predict stock returns cross‐sectionally in the international market. The significance of the trend strategy is associated with market‐level characteristics such as macroeconomic conditions, culture, and the information environment. The trend premium is more pronounced in markets with a more advanced macroeconomic status, a higher level of information uncertainty and individualism, and better accessibility to foreign investors. Nevertheless, the trend strategy only outperforms the momentum strategy in a relatively short horizon.
Comparative hospitalization risk for SARS‐CoV‐2 Omicron and Delta variant infections, by variant predominance periods and patient‐level sequencing results, New York City, August 2021–January 2022
Authors: Greene Sharon K. , Levin‐Rector Alison , Kyaw Nang T. T. , Luoma Elizabeth , Amin Helly , McGibbon Emily , Mathes Robert W. , Ahuja Shama D.
Published: November 2022

Background

Comparing disease severity between SARS‐CoV‐2 variants among populations with varied vaccination and infection histories can help characterize emerging variants and support healthcare system preparedness.

Methods

We compared COVID‐19 hospitalization risk among New York City residents with positive laboratory‐based SARS‐CoV‐2 tests when ≥98% of sequencing results were Delta (August–November 2021) or Omicron (BA.1 and sublineages, January 2022). A secondary analysis defined variant exposure using patient‐level sequencing results during July 2021–January 2022, comprising 1–18% of weekly confirmed cases.

Results

Hospitalization risk was lower among patients testing positive when Omicron (16,025/488,053, 3.3%) than when Delta predominated (8268/158,799, 5.2%). In multivariable analysis adjusting for demographic characteristics and prior diagnosis and vaccination status, patients testing positive when Omicron predominated, compared with Delta, had 0.72 (95% CI: 0.63, 0.82) times the hospitalization risk. In a secondary analysis of patients with sequencing results, hospitalization risk was similar among patients infected with Omicron (2042/29,866, 6.8%), compared with Delta (1780/25,272, 7.0%), and higher among the subset who received two mRNA vaccine doses (adjusted relative risk 1.64; 95% CI: 1.44, 1.87).

Conclusions

Hospitalization risk was lower among patients testing positive when Omicron predominated, compared with Delta. This finding persisted after adjusting for prior diagnosis and vaccination status, suggesting intrinsic virologic properties, not population‐based immunity, explained the lower severity. Secondary analyses demonstrated collider bias from the sequencing sampling frame changing over time in ways associated with disease severity. Representative data collection is necessary to avoid bias when comparing disease severity between previously dominant and newly emerging variants.
Identification of cuproptosis‐related lncRNAs for prognosis and immunotherapy in glioma
Authors: Wang Lin , Li Yunqian , Wang Yubo , Li Jia , Sun Yajuan , Chen Jiajun , Wang Ziqian
Published: November 2022

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis‐related genes have prognostic predictive value has not been clarified. In this study, uni‐/multi‐variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis‐related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high‐ and low‐risk groups. Either for grade 2–3 or for grade 4, glioma patients with high‐risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high‐risk group was functionally associated with immune responses and cancer‐related pathways. The high‐risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high‐risk group were significantly higher than those in the low‐risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T‐cell co‐stimulation pathways. In conclusion, we established a risk model based on cuproptosis‐related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno‐microenvironment status of glioma.
Medical management of small uterocutaneous fistulae with gonadotrophin releasing hormone analogs: Case report and literature review
Authors: Sanjuan Carles Raul , Sharif Shehzad , Rodriguez Arias Jesus , Berg Lauren , Nakhosteen Ali , Yoong Wai
Published: November 2022

Conventional management of uterocutaneous fistula involves open or laparoscopic excision as well as hysterectomy but there is now increasing recognition of successful medical treatment with gonadotrophin releasing hormone agonists. We describe the fourth case in the literature of successful nonsurgical treatment of uterocutaneous fistula and discuss two important factors affect the success of medical management, namely the size of the fistula and the duration of treatment. We would recommend that a trial of gonadotrophin releasing hormone analogues for at least 6 months particularly in cases of uterocutaneous fistula of 5 mm or less in diameter as this conservative treatment is likely to obviate the need for more hazardous surgical intervention.
The Virtue of Mortality
Authors: Flescher Andrew
Published: November 2022

As technology's frontiers advance, we acquire the capacity to alleviate the aspects of suffering and sorrow that are caused by our genetic programming, while also inviting unwelcome side consequences. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), a bacterial defense system with genome editing capabilities, is now being implemented to startling results. It is being used to correct for harmful mutations by permanently altering genes, promising to eliminate defects in whole species. Advantages notwithstanding, and apart from insufficiently considered dangers precipitated by the well‐intended technology, there are other moral issues to consider. What does existence look like in which humans become resistant to experiencing genetic defects? We can welcome medical innovation's reduction of undue hardship, but is there a threshold past which a permanently improved version of us makes us ineligible to participate in the human condition? This essay offers a theological and Aristotelian critique of using CRISPR for extensive human gene editing, arguing that it is our imperfections, including susceptibility to disease, decline due to aging, and the ephemerality of joy, which make us human.
A systematic review of dreams and nightmares recall in patients with rapid eye movement sleep behaviour disorder
Authors: Fasiello Elisabetta , Scarpelli Serena , Gorgoni Maurizio , Alfonsi Valentina , Galbiati Andrea , De Gennaro Luigi
Published: November 2022

Rapid eye movement (REM) sleep behaviour disorder is a REM sleep parasomnia characterised by the loss of the physiological muscle atonia during REM sleep, resulting in dream enactment behaviours that may cause injuries to patients or their bed partners. The nocturnal motor episodes seem to respond to the dream contents, which are often vivid and violent. These behavioural and oneiric features make the REM sleep behaviour disorder a potential model to study dreams. This review aims to unify the literature about dream recall in REM sleep behaviour disorder as a privileged approach to study dreams, systematically reviewing studies that applied retrospective and prospective experimental designs to provide a comprehensive overview of qualitative and quantitative aspects of dream recall in this REM sleep parasomnia. The present work highlights that the study of dreaming in REM sleep behaviour disorder is useful to understand unique aspects of this pathology and to explore neurobiological, electrophysiological, and cognitive mechanisms of REM sleep and dreaming.
Multiple arterial‐phase MRI with gadoxetic acid improves diagnosis of hepatocellular carcinoma ≤3.0 cm
Authors: Hong Seung Baek , Hong Sun , Choi Sang Hyun , Park Seo Young , Shim Ju Hyun , Kim So Yeon , Lee Seung Soo , Kim Suk
Published: November 2022

Background and Aims

Multiple arterial‐phase magnetic resonance imaging (MA‐MRI) was introduced to overcome the limitations of gadoxetic acid‐enhanced MRI, but its clinical impacts on hepatocellular carcinoma (HCC) diagnosis have not been well assessed. We investigated whether MA‐MRI with gadoxetic acid could improve the diagnosis of HCC ≤3.0 cm in comparison with single arterial‐phase MRI (SA‐MRI).

Methods

This retrospective study included 397 patients from two tertiary institutions who underwent gadoxetic acid‐enhanced MRI (243 patients with 271 lesions in cohort‐1 underwent SA‐MRI, and 154 patients with 166 lesions in cohort‐2 underwent MA‐MRI). The patients had 437 hepatic lesions ≤3.0 cm with pathologic confirmation. The arterial‐phase image quality and diagnostic performance of SA‐MRI and MA‐MRI were analysed and compared. To minimize the effects of selection bias because of potential confounding between the two groups, propensity score‐matching was additionally performed.

Results

MA‐MRI showed a significantly higher percentage of optimal arterial‐phase timing (94.2% vs. 74.5%, p < .001) and lower incidence of inadequate examinations (1.3% vs. 5.8%, p = .034) than SA‐MRI. MA‐MRI had a significantly higher non‐rim arterial‐phase hyperenhancement (APHE) detection rate (94.9% vs. 85.5%, p = .005) and sensitivity for diagnosing HCC (87.4% vs. 70.0%, p < .001) than SA‐MRI, but no significant difference in specificity (92.9% vs. 93.1%, p = .966). In 123 pairs of propensity score‐matched patients, MA‐MRI had significantly higher sensitivity (89.1% vs. 74.5%, p = .006) than SA‐MRI with equal specificity (92.3% vs. 92.3%, p > .999).

Conclusions

Compared with SA‐MRI, MA‐MRI with gadoxetic acid can detect more non‐rim APHE and significantly improve sensitivity for diagnosing HCC ≤3.0 cm, without a significant decrease in specificity.
Livestock management promotes bush encroachment in savanna systems by altering plant–herbivore feedback
Authors: Koch Franziska , Tietjen Britta , Tielbörger Katja , Allhoff Korinna T.
Published: November 2022

Savannas are characterized by the coexistence of two contrasting plant life‐forms: woody and herbaceous vegetation. During the last decades, there has been a global trend of an increase in woody cover and the spread of shrubs and trees into areas that were previously dominated by grasses. This process, termed bush encroachment, is associated with severe losses of ecosystem functions and typically difficult to reverse. It is assumed to be an example of a critical transition between two alternative stable states. Overgrazing due to unsustainable rangeland management has been identified as one of the main causes of this transition, as it can trigger several self‐reinforcing feedback loops. However, the dynamic role of grazing within such feedback loops has received less attention. We used a set of coupled differential equations to describe the competition between shrubs and grasses, as well as plant biomass consumption via grazing and browsing. Grazers were assumed to receive a certain level of care from farmers, so that grazer densities emerge dynamically from the combined effect of vegetation abundance and farmer support. We quantified all self‐reinforcing and self‐dampening feedback loops at play and analyzed their relative importance in shaping system (in‐)stability. Bistability, the presence of a grass dominated and a shrub dominated state, emerges for intermediate levels of farmer support due to positive feedback that arises from competition between shrubs and grasses and from herbivory. We furthermore demonstrate that disturbances, such as drought events, trigger abrupt transitions from the grass dominated to the shrub dominated state and that the system becomes more susceptible to disturbances with increasing farmer support. Our results thus highlight the potential of interaction networks in combinations with feedback loop analysis for improving our understanding of critical transitions in general, and bush encroachment in particular.
Consistent desires and climate change
Authors: Coren Daniel
Published: November 2022

Philosophers have described the human perspective on climate change as a perfect moral storm. I take a new angle on that storm: I argue that our relevant desires feature a particularly problematic case of seemingly consistent but genuinely inconsistent desires. We have, first, non‐indexical desires such as a desire to (make the sacrifices necessary to) stop polluting our environment at some point. We have, second, indexical desires such as a desire not to (make the sacrifices necessary to) stop polluting our environment this year. Our indexical and non‐indexical desires are inconsistent. Such inconsistency is obvious in most short‐term, individual cases such as when we need to make a dentist appointment. But when it comes to climate change, that inconsistency is masked by factors such as longevity and bitter divisions. This is, unfortunately, why humanity may continue putting off the collective action required to address climate change.
Emerging adults’ judgments about helping at home: Situational and experiential sources of variability
Authors: Martinez Marie Grace S. , Dahl Audun
Published: November 2022

Judgments and decisions about household helping affect how families function, and they develop through everyday experiences. Much prior research has examined stable individual differences in prosocial orientations, but such orientations also vary within individuals. The present work examined situational and experiential sources of variability in emerging adults’ judgments and reasoning about helping at home. The research assessed judgments and reasoning about household helping in events that were either hypothetical (Studies 1 and 2) or took place in participants’ own homes (Study 2). Participants’ judgments about helping incorporated moral, personal, and social‐conventional considerations and differentiated helping in one's own home from helping in another home. Participants’ past experiences with household helping predicted their judgments about helping. Findings supported the view that emerging adults’ judgments about household helping are informed by both situational considerations and personal experiences.
Static and dynamic spectral characteristics of Swedish voiceless fricatives
Authors: Wikse Barrow Carla , Włodarczak Marcin , Thörn Lisa , Heldner Mattias
Published: November 2022

Descriptions of the acoustic characteristics of Swedish voiceless fricatives are scarce and are limited to static measures derived from the speech of a small number of speakers. The current study provides an updated acoustic description of the static (spectral, temporal, and intensity) characteristics of word-initial voiceless fricatives in Central Standard Swedish. In addition, temporal variation of spectral centre of gravity is modelled using a generalized additive mixed model. Results show that fricatives were differentiated in terms of spectral properties, duration, and intensity level, such that sibilant fricatives were generally longer and more intense than non-sibilant fricatives. Spectral centre of gravity differentiated between all places of articulation apart from labio-dental /f/. Gender differences were found for centre of gravity in /s/ but overall, sex/gender differences were small. Dynamic analyses revealed differences in curvature as well as overall level of spectral centre of gravity across the duration of the fricative, associated with place of articulation and mediated by vowel context, fricative duration, and speaker specific patterns. The results from the present study are valuable for future cross-linguistic research, and as reference for investigations concerning children's acquisition of Swedish voiceless fricatives.
Recognizing the aeroacoustic information of noise radiated by an unflanged duct based on convolutional neural networks
Authors: Guo Jingwen , Li Xiangtian , Ren Chenyu , Zhang Xin
Published: November 2022

Accurately recognizing the aeroacoustic information of noise propagating into and radiating out of an aero-engine duct is of both fundamental and practical interest. The aeroacoustic information includes (1) the acoustic properties of the noise source, such as the frequency (f) and the circumferential and radial mode numbers (m, n), and (2) the flight conditions, including the ambient flow speed (M0) and the jet flow speed (M1). In this study, a data-driven model is developed to predict the aeroacoustic information of a simplified aero-engine duct noise from the far-field sound pressure level directivity. The model is constructed by the integration of one-dimensional convolutional layers and fully connected layers. The training and validation datasets are calculated from the analytical model for noise radiation from a semi-infinite unflanged duct based on the Wiener–Hopf method. For a single-spinning mode source, a regression model is established for f, M0, and M1 prediction, and a classification model is built up for m and n prediction. Additionally, for a multi-spinning mode source, the regression model is used to predict the coefficient of each mode. Results show that the proposed data-driven model can effectively and robustly predict the acoustic characteristics of noise propagation in and radiation out of an aero-engine bypass duct.
Rheology and self-healing of amine functionalized polyolefins
Authors: Yavitt B. M. , Tomkovic T. , Gilmour D. J. , Zhang Z. , Kuanr N. , van Ruymbeke E. , Schafer L. L. , Hatzikiriakos S. G.
Published: November 2022

The rheological and self-healing behavior of a class of catalytically synthesized amine-functionalized polyolefins is investigated. We demonstrate that these materials possess tunable rheological properties according to the molecular weight and display autonomous self-healing. The linear viscoelastic properties are modeled using a tube-based model developed by Hawke et al. [J. Rheol., 60, 297–310, (2016)] to calculate several model parameters that describe the individual chain dynamics. The self-healing response is described by findings from the reptation model as well as recent theory on associating polymer networks with reversible bonds. The cooperation between experiments, modeling, and theory provide insight into designing new materials with programmable rheological properties and superior self-healing ability.
Microrheological study of single chain dynamics in semidilute entangled flexible polymer solutions: Crossover from Rouse to Zimm modes
Authors: Indei Tsutomu , Narita Tetsuharu
Published: November 2022

The dynamics of polymer chains in entangled semidilute solution have been of theoretical and experimental interest. Among a number of characteristic lengths and times of the polymer in solution, those of the correlation blob are the key to understand the applicability of the Rouse and Zimm models to rheology of the semidilute solution. Direct rheological measurements of Rouse and Zimm modes are limited as the corresponding time scale is out of the range of classical rheological techniques. We investigated the single chain dynamics of entangled poly(ethylene oxide) in semidilute aqueous solutions by high-frequency micro-rheology based on diffusing-wave spectroscopy compared to classical shear macro-rheology. Concentration dependence of the three characteristic times of the entangled polymer chains, reptation time, entanglement time, and correlation time, was studied with the help of the time-concentration superposition. At the low frequency range, dynamic moduli measured by macro-rheology and micro-rheology showed a good agreement without adjustable parameters. At the higher frequency range, we found the Rouse regime in the mean square displacement of the probe particles and in the magnitude of the complex specific viscosity of the solution. We propose a simple method to estimate the boundary of the Rouse regime. Finally, at the high frequency range, we demonstrate that the contribution of the solvent to the solution viscosity needs to be subtracted to observe the power-law behavior of the Zimm mode.
A single-chain model for the linear viscoelasticity of unentangled melts of associating polymers
Authors: Liu Hongwei , Ianniruberto Giovanni , Marrucci Giuseppe
Published: November 2022

Existing single-chain models for unentangled associating polymers account for the association by assigning the sticky junctions a large value of the monomeric friction coefficient, which prevents them from moving in space unless stickers effectively dissociate. With such an assumption, comparison of model predictions with linear viscoelastic data is not fully successful in the intermediate range of frequency. In this work, we improve agreement with data by developing a single-chain model where sticky junctions are allowed to quickly move in space without dissociating. We also account for a random distribution of the stickers but differently from the recent model by Jiang et al. [Macromolecules 53, 3438–3451 (2020)]. Predictions of the model are successfully compared with unentangled melt data for two different copolymer chemistries and different sticker concentrations. Particularly significant are the data by Cui et al. [J. Rheol., 62, 1155–1174 (2018)] of melts of polymers with only two stickers per chain, revealing that sticky junctions are in fact also endowed with fast mobility.
Dynamics of entangled metallosupramolecular polymer networks combining stickers with different lifetimes
Authors: Li Yanzhao , Pyromali Christina , Zhuge Flanco , Fustin Charles-André , Gohy Jean-François , Vlassopoulos Dimitris , van Ruymbeke Evelyne
Published: November 2022

We study the linear viscoelastic properties of polymeric networks formed by poly(n-butyl acrylate) telechelic stars end-capped with 2,2:6,2″-terpyridine (Star-PnBA-tpy4) and two types of metal-ligand cross-links with different lifetimes. The influence of interactions, mediated by temperature, nature of metal ions, and ion content, on the linear viscoelastic behavior of both single and double dynamics transient networks is systematically investigated by small amplitude oscillatory shear and creep rheometry. The experimental results reveal that the dynamics of networks with two different metal-ligand cross-links is much faster than expected, characterized by the average sticker lifetime rather than a discrete contribution of each metal-ligand complex. We model the dynamics with the help of our modified tube-based time marching algorithm by accounting for both association/dissociation dynamics of metal-ligand coordination and the entanglement dynamics. Two parameters are defined in the model, namely, the proportion of dangling ends and the average time during which a sticker is free. This allows us to quantify the transient dynamics of the network and, in particular, to determine how the sticker dynamics depend on temperature and ion content.
Rheological investigation on the associative properties of poly(vinyl alcohol) solutions
Authors: Parisi Daniele , Ditillo Colin D. , Han Aijie , Lindberg Seth , Hamersky Mark W. , Colby Ralph H.
Published: November 2022

We report intrinsic viscosity and flow curve measurements on a set of five industrial poly(vinyl alcohol) (PVOH) samples, with varying degree of hydrolysis, molecular weight, and concentration in two solvents: water and dimethyl sulfoxide (DMSO). Aqueous poly(vinyl alcohol) solutions exhibit clear features of associative polymers, and the hydroxyl-carbonyl hydrogen bonds seem to dominate polymer chain associations. We propose a “sticky-blob” model, applicable to any associating polymer solution with many stickers inside each correlation blob, which predicts the concentration dependence of the specific viscosity and the chain relaxation time in the entanglement regime. When PVOH polymers are dissolved in DMSO, a strong hydrogen bond acceptor, chain-chain associations are fully prevented for all relevant degrees of hydrolysis. The specific viscosity and the relaxation time of the chain recover the expected concentration dependences for nonassociating flexible polymers in DMSO. The same concentration dependences are exhibited by literature data on 100% hydrolyzed PVOH in water, as the acetate content, dominating interchain associations, is zero. Comparing entangled aqueous and DMSO solutions at the same concentration enables the experimental measure of the time delay due to associations as the ratio between the terminal relaxation time of solutions in water and DMSO. The concentration dependence of such a time delay was also captured by the simple sticky-blob model introduced in this work.
Fracture of dual crosslink gels with permanent and transient crosslinks: Effect of the relaxation time of the transient crosslinks
Authors: Zhao Jingwen , Debertrand Louis , Narita Tetsuharu , Creton Costantino
Published: November 2022

We investigate the fracture properties of poly(acrylamide-co-1-vinylimidazole) dual crosslink hydrogels [P(AAm-co-VIm)-M2+ gels] containing a small fraction of covalent bonds and a majority of dynamic bonds based on metal coordination bonds (Ni2+ or Zn2+). Unlike a previous study on a different dual crosslink hydrogel system having slower dynamic bonds based on poly(vinylalcohol) and borate ions (PVA-Borax gels), the presence of these faster dynamic coordination bonds has two main effects: They significantly toughen the P(AAm-co-VIm)-M2+ gels even at high stretch rates, where the dynamic bonds should in principle behave as covalent bonds at the crack tip, and they toughen the gels at very low stretch rates, where the dynamic bonds are invisible during the loading stage. We propose two additional molecular mechanisms to rationalize this behavior of P(AAm-co-VIm)-M2+ gels: we hypothesize that fast exchanging dynamic bonds remain slow compared to the characteristic time of bond scission and are, therefore, able to share the load upon covalent bond scission even at low loading rates. We also argue of the existence of longer-lived clusters of dynamic bonds that introduce a stretch rate-dependent strain hardening in uniaxial tension and stabilize and increase the size of the dissipative zone at the crack tip, thereby introducing a strain-dependent dissipative mechanism.
In vitro and in vivo efficacy of tecovirimat against a recently emerged 2022 monkeypox virus isolate
Authors: Warner Bryce M. , Klassen Levi , Sloan Angela , Deschambault Yvon , Soule Geoff , Banadyga Logan , Cao Jingxin , Strong James E. , Kobasa Darwyn , Safronetz David
Published: November 2022

The recent emergence of the monkeypox virus (MPXV) in non-endemic countries has been designated a Public Health Emergency of International Concern by the World Health Organization. There are currently no approved treatments for MPXV infection in the United States or Canada. The antiviral drug tecovirimat (commonly called TPOXX), previously approved for smallpox treatment, is currently being deployed for treatment of MPXV infections where available based on previously accrued data. We tested the efficacy of TPOXX both in vitro and in vivo against a clade 2 Canadian 2022 isolate of MPXV isolated during the current outbreak. TPOXX prevented MPXV replication in vitro with an effective concentration in the nanomolar range. To evaluate TPOXX efficacy in vivo, we first characterized the CAST/EiJ mouse model with the same 2022 Canadian isolate. Unlike previous descriptions of this model, the Canadian isolate was not lethal in CAST/EiJ mice, although it replicated efficiently in the respiratory tract after intranasal infection. Subsequent experiments demonstrated that daily oral TPOXX treatment markedly reduced viral titers in the tissues 1 and 2 weeks after infection. Our data indicate that TPOXX is highly effective against currently circulating MPXV strains and could be an important contributor to curbing the ongoing outbreak.
Embolisation of iatrogenic lumbar artery bleed causing psoas haematoma following elective lumbar puncture
Authors: Oladeji Emmanuel , Rati Kuran , Rakhimova Kamila , Day Nigel
Published: November 2022

The case of a female patient in her 50s presenting as a surgical emergency with abdominal pain and a positive Obraztsova’s sign. Seven days prior to the presentation, a lumbar puncture (LP) had been performed to investigate severe headaches and exclude a subarachnoid haemorrhage. The patient was subsequently found to have an acute lumbar arterial bleed causing haemodynamic instability and a psoas haematoma. An emergency lumbar artery embolisation procedure was performed by the interventional radiology department in order to stabilise the bleed. The patient made a full recovery prior to discharge.
Tumour-induced osteomalacia due to a durally-based intracranial phosphaturic mesenchymal tumour
Authors: Shand James Allan Douglas , Kim David
Published: November 2022

A man in his 40s was referred with persistent hypophosphataemia and bony pain. A serum fibroblast growth factor 23 level was markedly elevated and a diagnosis of tumour-induced osteomalacia was considered. Whole body imaging revealed multiple insufficiency fractures but no osseus tumours. There was, however, a durally-based intracranial lesion whose imaging characteristics were consistent with a meningioma. The tumour was removed, leading to rapid normalisation of the patient’s symptoms and serum markers. Histology confirmed a phosphaturic mesenchymal tumour. We review the literature regarding this rare clinical situation.
New insights intoCC2D2A-related Joubert syndrome
Authors: Harion Madeleine , Qebibo Leila , Riquet Audrey , Rougeot Christelle , Afenjar Alexandra , Garel Catherine , Louha Malek , Lacaze Emmanuelle , Audic-Gérard Frédérique , Barth Magali , Berquin Patrick , Bonneau Dominique , Bourdain Frédéric , Busa Tiffany , Colin Estelle , Cuisset Jean-Marie , Des Portes Vincent , Dorison Nathalie , Francannet Christine , Héron Bénédicte , Laroche Cécile , Lebrun Marine , Métreau Julia , Odent Sylvie , Pasquier Laurent , Trujillo Yaumara Perdomo , Perrin Laurine , Pinson Lucile , Rivier François , Sigaudy Sabine , Thauvin-Robinet Christel , Louvier Ulrike Walther , Labayle Olivier , Rodriguez Diana , Valence Stéphanie , Burglen Lydie
Published: November 2022

Purpose

In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes,CC2D2A.

Methods

We selected 53 patients with pathogenic variants onCC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.

Results

Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype–phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype.

Conclusion

This study contradicts previous literature stating an association betweenCC2D2A-related JS and ventriculomegaly. Our study implies thatCC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.