bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epimorphic regeneration of the mouse digit tip is finite
Authors: Dolan Connor P. , Yang Tae-Jung , Zimmel Katherine , Imholt Felisha , Qureshi Osama , Falck Alyssa , Gregory Joshua , Mayes Macie , Ritchie Kayla , Koester Hannah , Daniel Benjamin , Yan Mingquan , Yu Ling , Suva Larry J. , Gaddy Dana , Dawson Lindsay A. , Muneoka Ken , Brunauer Regina 
Published: February 2022

AbstractBackgroundStructural regeneration of amputated appendages by blastema-mediated, epimorphic regeneration is a process whose mechanisms are beginning to be employed for inducing regeneration. While epimorphic regeneration is classically studied in non-amniote vertebrates such as salamanders, mammals also possess a limited ability for epimorphic regeneration, best exemplified by the regeneration of the distal mouse digit tip. A fundamental, but still unresolved question is whether epimorphic regeneration and blastema formation is exhaustible, similar to the finite limits of stem-cell mediated tissue regeneration.MethodsIn this study, distal mouse digits were amputated, allowed to regenerate and then repeatedly amputated. To quantify the extent and patterning of the regenerated digit, the digit bone as the most prominent regenerating element in the mouse digit was followed by in vivo µCT.ResultsAnalyses revealed that digit regeneration is indeed progressively attenuated, beginning after the second regeneration cycle, but that the pattern is faithfully restored until the end of the fourth regeneration cycle. Surprisingly, when unamputated digits in the vicinity of repeatedly amputated digits were themselves amputated, these new amputations also exhibited a similarly attenuated regeneration response, suggesting a systemic component to the amputation injury response.ConclusionsIn sum, these data suggest that epimorphic regeneration in mammals is finite and due to the exhaustion of the proliferation and differentiation capacity of the blastema cell source.
Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy
Authors: Martinez-Valbuena Ivan , Visanji Naomi P. , Kim Ain , Lau Heather H. C. , So Raphaella W. L. , Alshimemeri Sohaila , Gao Andrew , Seidman Michael A. , Luquin Maria R. , Watts Joel C. , Lang Anthony E. , Kovacs Gabor G. 
Published: February 2022

Abstract
Background
Multiple system atrophy (MSA) is a neurodegenerative condition characterized by variable combinations of parkinsonism, autonomic failure, cerebellar ataxia and pyramidal features. Although the distribution of synucleinopathy correlates with the predominant clinical features, the burden of pathology does not fully explain observed differences in clinical presentation and rate of disease progression. We hypothesized that the clinical heterogeneity in MSA is a consequence of variability in the seeding activity of α-synuclein both between different patients and between different brain regions.

Methods
The reliable detection of α-synuclein seeding activity derived from MSA using cell-free amplification assays remains challenging. Therefore, we conducted a systematic evaluation of 168 different reaction buffers, using an array of pH and salts, seeded with fully characterized brain homogenates from one MSA and one PD patient. We then validated the two conditions that conferred the optimal ability to discriminate between PD- and MSA-derived samples in a larger cohort of 40 neuropathologically confirmed cases, including 15 MSA. Finally, in a subset of brains, we conducted the first multi-region analysis of seeding behaviour in MSA.

Results
Using our novel buffer conditions, we show that the physicochemical factors that govern the in vitro amplification of α-synuclein can be tailored to generate strain-specific reaction buffers that can be used to reliably study the seeding capacity from MSA-derived α-synuclein. Using this novel approach, we were able to sub-categorize the 15 MSA brains into 3 groups: high, intermediate and low seeders. To further demonstrate heterogeneity in α-synuclein seeding in MSA, we conducted a comprehensive multi-regional evaluation of α-synuclein seeding in 13 different regions from 2 high seeders, 2 intermediate seeders and 2 low seeders.

Conclusions
We have identified unexpected differences in seed-competent α-synuclein across a cohort of neuropathologically comparable MSA brains. Furthermore, our work has revealed a substantial heterogeneity in seeding activity, driven by the PBS-soluble α-synuclein, between different brain regions of a given individual that goes beyond immunohistochemical observations. Our observations pave the way for future subclassification of MSA, which exceeds conventional clinical and neuropathological phenotyping and considers the structural and biochemical heterogeneity of α-synuclein present. Finally, our methods provide an experimental framework for the development of vitally needed, rapid and sensitive diagnostic assays for MSA.
Insights into the role of major bioactive dietary nutrients in lamb meat quality: a review
Authors: Álvarez-Rodríguez Javier , Urrutia Olaia , Lobón Sandra , Ripoll Guillermo , Bertolín Juan Ramón , Joy Margalida 
Published: February 2022

AbstractFeed supplementation with α-linolenic acid (ALA) and linoleic acid (LA) increases their content in muscle, ALA increases n-3 polyunsaturated fatty acids and decrease n-6/n-3 ratio in muscle, and LA increases rumenic acid. However, high LA supplementation may have negative effects on lambs’ lipid oxidative stability of meat. When the sources of ALA and LA are fed as fresh forage, the negative effects are counterbalanced by the presence of other bioactive compounds, as vitamin E (mainly α-tocopherol) and polyphenols, which delay the lipid oxidation in meat. There is a wide consensus on the capability of vitamin E delaying lipid oxidation on lamb meat, and its feed content should be adjusted to the length of supplementation. A high dietary inclusion of proanthocyanidins, phenolic compounds and terpenes reduce the lipid oxidation in muscle and may improve the shelf life of meat, probably as a result of a combined effect with dietary vitamin E. However, the recommended dietary inclusion levels depend on the polyphenol type and concentration and antioxidant capacity of the feedstuffs, which cannot be compared easily because no routine analytical grading methods are yet available. Unless phenolic compounds content in dietary ingredients/supplements for lambs are reported, no specific association with animal physiology responses may be established.
Estimated glomerular filtration rate in Korean patients exposed to long-term lithium maintenance therapy
Authors: Cho Yunji , Lee Dongbin , Baek Ji Hyun , Hong Kyung Sue 
Published: February 2022

Abstract
Background
Lithium-induced nephrotoxicity has long been debated. However, it has been rarely explored in Asian populations. The aim of the present study was to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eGFR) in Korean patients diagnosed with a psychiatric illness.

Methods
This was a single-centered, retrospective study that included patients treated with lithium or comparator drug (valproate) in Samsung Seoul Medical Center between November 1994 and July 2020. Patients diagnosed with ICD codes F20-33 who had  ≥ 6 months of exposure to lithium or valproate were included. Patients had to have  ≥ 1 baseline and  ≥ 2 post-baseline eGFR data with post-baseline data having an interval of at least 30 days. Chronic kidney disease (CKD) was defined as CKD stage 3 (eGFR  < 60 mL/min/1.732). To be considered as CKD, the threshold had to be met at two consecutive post-baseline measurements. Those treated with both lithium and valproate, diagnosed with CKD stages 3–5, diagnosed with a renal disease, or received kidney transplantation were excluded.

Results
A total of 766 patients were included (242 treated with lithium and 524 with valproate). Two (0.8%) in the lithium group and 8 (1.5%) in the valproate group developed CKD stage 3. None developed CKD stages 4–5. Median yearly eGFR change was − 1.3 mL/min/1.732 (IQR: − 6.8, 1.7) for the lithium group and − 1.1 mL/min/1.732 (IQR: − 4.5, 1.5) for the valproate group, showing no significant difference between the two groups (p  = 0.389). The rate of decline was more rapid for those with CKD in both groups. eGFR values of lithium and valproate groups did not show significant differences during a follow-up duration of 15 years or more. A significant negative correlation between baseline eGFR and yearly eGFR change was identified in a linear regression analysis.

Conclusions
In Korean patients, treatment with lithium did not increase the risk of developing CKD compared to treatment with valproate. Prevalence of CKD was lower than those previously reported in western populations. Low baseline eGFR showed significant correlation with changes in renal function.
The ripple effect, silence and powerlessness: hidden barriers to discussing suicide in Australian Aboriginal communities
Authors: Heard Todd R. , McGill Katherine , Skehan Jaelea , Rose Bronwyn 
Published: February 2022

AbstractBackgroundSuicide is one of the leading causes of death for Aboriginal Australians. There is an urgent need to actively engage with Aboriginal communities to better understand these issues and to develop solutions together to prevent deaths by suicide in Aboriginal communities.MethodsUtilising a qualitative, thematic, cross-sectional design, we conducted focus groups in three communities in the Hunter New England area in New South Wales (Australia) to explore the perceptions and views of Aboriginal participants in relation to discussing suicide.ResultsThe key themes found to influence discussions about suicide in Aboriginal communities included the sense that suicide is a whole of community issue, the ripple effect of suicide deaths, silence about suicide and the impact of this silence, and being powerless to act. Participants described a reluctance to have discussions about suicide; feeling they had limited skills and confidence to have these sorts of discussions; and multiple and interrelated barriers to discussing suicide, including shame, fear and negative experiences of mental health care. Participants also described how their experiences maintained these barriers and prevented Aboriginal Australians from seeking help in suicidal crises.ConclusionFuture initiatives should address the interrelated barriers by supporting Aboriginal people to build skills and confidence in discussing suicide and mental health and by improving access to, and the experience of, mental health care and psychosocial and community-based supports for Aboriginal Australians. We suggest trying to address any one of these factors in isolation may increase rather than decrease suicide risk in Aboriginal communities.
Narrow and wide India–Burma trough-like circulations: their different impacts on precipitation over southern China
Authors: Li Jing-Xin , Liu Ge , Wu Renguang , Ren Hong-Li , Wang Hui-Mei , Mao Xin , Wei Xin-Chen 
Published: February 2022

AbstractThe India–Burma troughs (IBTs) with different shapes (i.e., narrow and wide IBT-like circulations) can significantly affect winter precipitation over different regions in southern China through modulating the paths of water vapor transportation ahead of the IBTs. The effect of the wide/narrow IBT- (WIBT/NIBT-) like circulation cannot be depicted by traditional IBT indices that mainly focus on the IBT’s intensity. This study defines the WIBT and NIBT indices, which can effectively distinguish different water vapor transportation in front of the WIBT and NIBT and relevant water vapor convergence and therefore successfully reflect different distributions of winter precipitation anomalies over southern China. Further exploration reveals that a Rossby wave from the Mediterranean Sea to the Bay of Bengal (BoB) contributes to the variability of the NIBT, while the El Niño–Southern Oscillation (ENSO) can modulate the variability of the WIBT by stimulating the Matsuno–Gill response. The WIBT and NIBT indices should be considered as important supplements to the traditional IBT indices, which are favorable to more detailed diagnosis and prediction of winter climate over southern China.
The role of diosgenin in crohn’s disease
Authors: Ogundepo Sunday , Chiamaka Adinnu M. , Olatinwo Mercy , Adepoju David , Aladesanmi Matthias Taiwo , Celestine Ugwu Obiora , Ali Kingsley Chijioke , Umezinwa Ogochukwu Jennifer , Olasore Janet , Alausa Abdullahi 
Published: February 2022

AbstractInflammatory bowel disease (IBD) is a chronic idiopathic inflammation that can grossly affect the entire gastrointestinal tract (GIT) from the mouth to the anus. Crohn’s disease is the most known type of IBD and has been the focus of attention due to its increase in prevalence worldwide. Although the etiology is yet to be elucidated, recent studies have pointed out Crohn’s disease to arise from a complex interaction between environmental influences, genetic predisposition, and altered gut microbiota, resulting in dysregulated adaptive and innate responses. The presenting hallmarks of Crohn’s disease may include weight loss, nausea, vomiting, abdominal pain, diarrhea, fever, or chills. Treatment is usually done with many approved immunosuppressive drugs and surgery. However, a promising avenue from natural compounds is a safer therapy due to its safe natural active ingredients and the strong activity it shows in the treatment and management of diseases. Diosgenin, “a major biologically active natural steroidal sapogenin found in Chinese yam,” has been widely reported as a therapeutic agent in the treatment of various classes of disorders such as hyperlipidemia, inflammation, diabetes, cancer, infection, and immunoregulation. In this review, an analysis of literature data on diosgenin employed as a therapeutic agent for the treatment of Crohn’s disease is approached, to strengthen the scientific database and curtail the dreadful impact of Crohn’s disease.
Epizootics of entomopathogenic fungi at overwintering sites of Oebalus mexicana Sailer (Hemiptera: Pentatomidae) from Western Mexico
Authors: Cortez-Madrigal Hipolito , Montores-Ramírez Joel , Cárdenas-Ochoa Cecilia , Ochoa-Echegollen Mónica 
Published: February 2022

AbstractBackgroundOebalus mexicanaSailer (Hemiptera: Pentatomidae) is an important pest of sorghum in Central-Western Mexico. In addition to damaging the grain, it is a vector of the panicle blight,Fusarium moniliforme.Oebalus mexicanahibernates at > 2200 m above sea level (masl), and its control in these sites is through entomopathogenic fungi (EPF). Their effectiveness could be misperceived as natural epizootics at hibernation sites. To characterize fungal epizootics associated with hibernating adults ofO. mexicana, during 2019 and part of 2020, a study was established in the Zináparo hill, Michoacan, Mexico. Three sampling strata were defined—two at low (2219 masl) and high levels of elevation (2351 masl), and another one at intermediate elevation (2244 masl) and soil humidity most of the year. Under the leaf litter, live arthropods and corpses with and without mycosis were recorded every 2 weeks; associated EPF were isolated and identified. Soil humidity, temperature, and RH under the litter were recorded.ResultsSix genera of fungi were identified, withBeauveriabeing the most prevalent. Mortality ofO. mexicanain the field was > 80%, with a high correlation (r = 0.85–0.97) with mortality due to fungi (> 65%). The humidity of soil and litter created a suitable environment for the development of epizootics. The highest prevalence was registered at the elevations of 2244, 2351, and 2219 masl, respectively. More than 15 families of arthropods were registered, several of them with the presence of mycosis. Their permanence as alternate hosts contributed to the persistence of the fungi. Field and laboratory evidences suggested that the frequent flights ofO. mexicanafavoured the self-dissemination of EPF. Thus, more than 37% of live individuals with inoculum and subsequent infection and death were recorded.ConclusionsThe EPF disease at overwintering sites ofO. mexicanawas enzootic, and under favourable conditions it can become epizootic. The high levels of natural control in hibernation sites suggest that additional control measures forO. mexicanaare unnecessary; on the contrary, the conservation of these sites as reservoirs of EPF is proposed for a sustainable use in the management of this and other pests.
Validation of an epilepsy management smartphone application in Pakistan
Authors: Patterson Victor , Larik Awais Bashir , Soomro Mohamed Zaman , Coates Steve 
Published: February 2022

Abstract
Background
There is no single way to improve epilepsy care in low- and middle-income countries (LMICs). An epilepsy management aid application (app) has been described, which enables a non-physician health worker (NPHW) to communicate with an epilepsy specialist using a smartphone. In this study, we aimed to assess the validity and quality of this care system in building connections between NPHWs and specialists in Pakistan and the UK.

Methods
A NPHW in Pakistan used the app on a series of referrals and sent the app-generated summary by email to a neurologist in the UK, who replied and suggested possible management. Patients were later seen in a face-to-face (FF) manner by the UK neurologist and a local neurologist, and diagnostic accuracy and quality parameters were assessed.

Results
Over 10 months, 59 patients were recruited and 33 of them were available for FF assessment. The misdiagnosis rate of the app was 6% (2 cases). Treatment advice provided by the app was judged appropriate in 32 patients (97%). In addition, 46% of the referrals were completed within 2 h and 85% within 24 h.

Conclusions
Consistent with an earlier study, this system is a safe method to provide care for patients who cannot access neurological services in person. In addition, it has advantage of timeliness compared to FF assessment and requires less specialist time, both of which are especially important during the coronavirus disease 2019 pandemic. This system can be generalised easily, depending on the willingness of referrers and specialists to use it.
Intraoperative Hypotension and Myocardial Injury After Noncardiac Surgery in Adults With or Without Chronic Hypertension: A Retrospective Cohort Analysis
Authors: Cohen Barak , Rivas Eva , Yang Dongsheng , Mascha Edward J. , Ahuja Sanchit , Turan Alparslan , Sessler Daniel I. 
Published: February 2022

BACKGROUND:
The risk of myocardial injury progressively increases at intraoperative mean arterial pressures (MAPs) ≤65 mm Hg. Higher pressures might be required in chronically hypertensive patients. We aimed to test the hypothesis that the harm threshold is higher in patients with chronic hypertension than in normotensive patients.

METHODS:
We conducted a single-center retrospective cohort analysis of adults >45 years old who had noncardiac surgery between 2010 and 2018 and scheduled, rather than symptom-driven, postoperative troponin measurements. The MAP thresholds under which risk started to increase were compared between patients with chronic hypertension (baseline MAP ≥110 mm Hg) and normotensive patients (baseline MAP <110 mm Hg). The primary outcome was a composite of in-hospital mortality and myocardial injury within 30 days, defined by any postoperative 4th-generation troponin T measurement ≥0.03 ng/mL apparently due to cardiac ischemia. Multivariable logistic regression and moving average smoothing methods were used to evaluate confounder-adjusted associations between the composite outcome and the lowest intraoperative MAP sustained for either 5 or 10 cumulative minutes, and whether the relationship depended on baseline pressure (normotensive versus hypertensive).

RESULTS:
Among 4576 eligible surgeries, 2066 were assigned to the normotensive group with mean (standard deviation [SD]) baseline MAP of 100 (7) mm Hg, and 2510 were assigned to the hypertensive group with mean baseline MAP of 122 (10) mm Hg. The overall incidence of the composite outcome was 5.6% in normotensive and 6.0% in hypertensive patients (P = .55). The relationship between intraoperative hypotension and the composite outcome was not found to depend on baseline MAP in a multivariable mixed effects logistic regression model. Furthermore, no statistical change points were found for either baseline MAP group.

CONCLUSIONS:
Baseline blood pressure of the hypertensive patients was only moderately increased on average, and the event rate was low. Nonetheless, we were not able to demonstrate a difference in the harm threshold between normotensive and chronically hypertensive patients. Our results do not support the theory that hypertensive patients should be kept at higher intraoperative pressures than normotensive patients.
Age-Related Recovery of Daily Living Activity After 1-Stage Complete Corpus Callosotomy: A Retrospective Analysis of 41 Cases
Authors: Ukishiro Kazushi , Osawa Shin-ichiro , Iwasaki Masaki , Kakisaka Yosuke , Jin Kazutaka , Uematsu Mitsugu , Yamamoto Tetsuya , Tominaga Teiji , Nakasato Nobukazu 
Published: February 2022

BACKGROUND:
Recovery time after corpus callosotomy (CC) is known to be longer in elderly than in younger patients.

OBJECTIVE:
To evaluate the relationship between patient age and recovery time of activities of daily living (ADL) after 1-stage complete CC.

METHODS:
This study included 41 patients (22 women; aged 13 months-34 years, median 7 years) who underwent 1-stage complete CC for medically intractable seizures with drop attacks, infantile spasms, and/or bilaterally synchronized electroencephalographic discharges between August 2009 and April 2019. The timing of restart of competence in 5 ADL categories and surgical outcomes were recorded.

RESULTS:
Patients (1) restarted speech at 2.2 ± 1.3 (mean ± 2 standard deviations; range 1-5) days, (2) restarted replying with their own name on request at 5.5 ± 8.6 (2-33) days, (3) restarted oral intake at 1.6 ± 1.7 (1-11) days, (5) discontinued intravenous feeding at 6.0 ± 3.0 (2-16) days, and (5) restarted ambulation or wheelchair movement at 5.8 ± 3.4 (2-10) days. Younger patients showed significantly (P < .0223) earlier recovery of ambulation or wheelchair movement, but no age difference was found in the other 4 ADL categories. Overall seizure freedom was achieved in 5 patients, excellent (>80%) seizure reduction in 11, good (50%-80%) seizure reduction in 5, and poor (<50%) seizure reduction in 20.

CONCLUSION:
Early ADL recovery after 1-stage complete CC is favorable in both young and adult patients. These findings, with good surgical outcomes, will encourage more positive consideration of 1-stage complete CC in both pediatric and adult patients.