bluuebunny/crossref_metadata_2025 huggingface dataset:
Locating power in party leader selection
Authors: Aylott Nicholas , Bolin Niklas
Published: December 2022

In this article, the aim is to enhance our understanding of who has power over leader selection in political parties. To this end, we apply an analytical framework in which the selection process is divided into three phases: gatekeeping, preparation and decision. The focus is on determining the extent to which each of these phases is influential for the outcome and thereby locating the distribution of intra‐party power. Underpinning the analysis is the conviction that the comparison of leader selection is too limited if it relies solely on information about formal procedures, including the composition of the selectorate. We should also take the preselection phase of leader selection into account. Empirically, we examine a sample of recent selection processes in European parliamentary democracies. In contrast to previous research on intra‐party politics, which has suggested an ascendancy of the party in public office, our results suggest an enduring strength of the party on the ground and the party in the central office.
Chemotherapy: A partnership with immunotherapy in non‐small cell lung cancer
Authors: Mendes Ana Sofia , Romão Raquel , Febra Joana , Azevedo Sérgio Xavier , Fidalgo Paula , Araújo António
Published: December 2022

Chemotherapy (CT) and immunotherapy (IO) act synergically in the treatment of non‐small cell lung cancer (NSCLC). However, the molecular basis of such interaction is poorly understood. The aim of this review was to explore the mechanisms of CT to potentiate the immune system and, consequently, the action of IO. The most up‐to‐date knowledge concerning the interaction of CT and IO in NSCLC was reviewed and a bibliographic search was made in PubMed/Medline database, using the mentioned keywords, with preference given to recently published articles in English.

In addition to the direct cytotoxic effect, CT affects the immune system leading indirectly to cell death. The immune response triggered by PD‐1 inhibition is enhanced by the cytotoxic immunogenic effects of CT. This potentiation phenomenon occurs due to an increase in effector cells relatively to regulatory cells, inhibition of myeloid derived suppressor cells, increased potential for cross‐presentation by dendritic cells after the death of tumor cells or blocking the STAT6 pathway to increase dendritic cell activity.

In conclusion, the effects of CT on the immune system work in synergy with the actions of IO, transforming “cold” tumors into “hot” tumors, which are more visible to the immune system.
Serum miR‐146a level is a potential biomarker in predicting the outcome of diffuse large B‐cell lymphoma
Authors: Huang Xin , Gui Ailing , Zhou Yi , Xia Zuguang , Liu Wen , Zuo Ji , Yang Ling , Zhang Qunling
Published: December 2022

Background

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma with heterogenicity in clinical manifestation and prognosis. Some microRNAs can influence the development of tumors and may be related to the response of therapy or prognosis. This study aims to explore the role of serum miR‐146a in predicting the prognosis of DLBCL.

Methods

A total of 72 de novo DLBCL patients received 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab combined CHOP (R‐CHOP) regimen, and their serum samples were collected before treatment and after 4 cycles of chemotherapy.

Results

The results show that a high level of miR‐146a is significantly associated with a good outcome in baseline and is more obvious in post‐chemotherapy. In addition, a high level of miR‐146a was associated with better progression‐free survival and overall survival in patients treated with R‐CHOP but has not been related to a superior outcome in patients treated with CHOP. Rituximab may improve the efficacy of therapy, especially in patients with high miR‐146a levels. The level of miR‐146a decreased in more patients after chemotherapy, and it seems patients with a decreased expression of miR‐146a after chemotherapy tended a better outcome, but it is not statistically significant.

Conclusion

Our results suggest that the level of serum miR‐146a can serve as a potential prognostic biomarker for DLBCL patients.
Transcriptomic analysis of mid‐secretory endometrium reveals essential immune factors associated with pregnancy after single euploid blastocyst transfer
Authors: Cheng Yanfei , Wang Hui , Shang Jin , Wang Jue , Yin Jingwen , Zhang Jinning , Guo Xinmeng , Wang Sidong , Duan Yong‐Gang , Lee Cheuk‐Lun , Chiu Philip C. N. , Zhang Jian , Yeung William S. B. , Cao Dandan , Yao Yuanqing
Published: December 2022

Purpose

Implantation is a limiting factor for treatment success in assisted reproduction. Both embryonic and endometrial factors contribute to implantation. Embryonic factors have often been ignored in previous studies about the role of endometrium in implantation. In this study, we sought to identify the endometrial genes associated with negative pregnancy outcomes following the transfer of a single euploid blastocyst.

Methods

Computational analyses of the transcriptomes of mid‐secretory endometria from nine pregnant and seven non‐pregnant patients in a cycle preceding the transfer of a single euploid blastocyst in a vitrified‐warmed cycle were performed.

Results

Principal component analysis of two reported endometrial receptivity gene sets showed close clustering of the pregnant and non‐pregnant samples. Differential gene expression analysis and co‐expression module analysis identified 131 genes associated with the pregnancy status. The endometrial signatures identified highlight the importance of immune and metabolic regulation in pregnancy outcome. Network analysis identified 20 hub genes that could predict pregnancy outcomes with 88.9% sensitivity and 85.7% specificity. Single‐cell gene expression analysis highlighted the regulation of endometrial natural killer (NK) cells, T cells, and macrophages during embryo implantation. Immune cell abundance analysis supported the dysregulation of cytotoxic immune cells in the endometria of non‐pregnant women.

Conclusions

We reported the first endometrial gene signature associated with pregnancy after elimination of embryo aneuploidy and highlighted the importance of the endometrial immune microenvironment and metabolic status in pregnancy outcomes.
Requesting air ambulance transport of patients with suspected appendicitis: The decision‐making process through the eyes of the rural clinician
Authors: Edwards Kristin H. , Franklin Richard C. , Edwards Mark T. , Stewart Ruth A.
Published: December 2022

Objective

The primary aim is to explore rural clinicians' self‐reported knowledge, skills and attitudes in the decision‐making process for requesting aeromedical retrieval of patients with suspected appendicitis. A secondary aim is to understand the supports and barriers of rural clinicians experience in this clinical scenario.

Setting

Clinician interviews conducted face‐to‐face in three rural hospitals in Central Queensland.

Participants

Rural doctors and nurses.

Design

A five‐part qualitative content analysis.

Results

The majority of 44 participants identified the strong and effective teamwork. The decision to request aeromedical retrieval was a shared, joint process and identified a supportive collegial culture which supported the asking of questions and not expecting to have all the answers. Perceived barriers were lack of receiving clinicians understanding of transfer agreements, and data connectivity. Clinician pessimism was identified for perceived patient outcomes.

Discussion

Effective teamwork can nurture trust and collaboration across multiple health service roles. High job satisfaction may counter the physical isolation in some rural environments. Fragmentation of care is the unintended consequence of interhospital transfer and may impact rural clinicians' perception of patients' outcomes and hinder receiving clinicians' understanding of rural service limitations.

Conclusion

Future work in the area of linked electronic medical records could remove a barrier for rural clinicians and improve their reflective practice by challenging their perception of definitive patient outcomes. Increased awareness by receiving clinicians of the limitation of rural services, may minimize communication barriers and thereby, improve timely patient care transfers.
Delayed haemolytic transfusion reaction in paediatric patients with sickle cell disease: A retrospective study in a French national reference centre
Authors: Rossi Marica , Pirenne France , Le Roux Enora , Smaïne Djamel , Belloy Marie , Eyssette‐Guerreau Stéphanie , Couque Nathalie , Holvoet Laurent , Ithier Ghislaine , Brousse Valentine , Koehl Bérengère , Faye Albert , Benkerrou Malika , Missud Florence
Published: December 2022

Delayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×109/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke (two patients) and kidney failure (two patients). A further transfusion was required in 23 patients and corticosteroids were used in 21 to reduce the risk of additional haemolysis. In all, 13 patients subsequently received further transfusions with recurrence of DHTR in only two. The study affords a better overview of DHTR and highlights the need to establish guidelines for its management in children.
Perceptions of dental students, dental faculty, practicing dentists and industry dental professionals on the acquisition of dental competencies and clinical skills in the Dominican Republic
Authors: Reyes Alardo Laura Virginia , Palmer Louann Bierlein , Beach Andrea , García‐Godoy Franklin
Published: December 2022

Introduction

This study gathered perceptions from four stakeholder groups in the Dominican Republic (DR) regarding acquiring professional dental competencies and clinical skills.

Materials and Methods

Researcher‐created surveys covering core dental competencies and clinical skills were distributed to stakeholder groups associated with nine different DR dental programs. Respondents included 153 undergraduate dental students, 153 dental faculty members, 108 practicing dentists (who had graduated in the past 5 years) and 42 industry professionals (who hire and supervise dentists). Data were examined using descriptive statistics, univariate ANOVA and multiple linear regressions.

Results

Dental school students and recent graduates now practicing dentists in the DR reflected moderate to solid confidence that they had learned most of the dental skills and competencies covered in the survey. Industry professionals were a bit less confident overall, while dental faculty offered the lowest scores, although those were often still in the moderately confident range. ANOVAs revealed significant differences when broken down by individual university dental programs. Regressions also revealed that individual university dental programs significantly predict confidence that dental skills and competencies were achieved.

Conclusion

Data show that DR's dental stakeholder groups generally felt optimistic about the learning occurring. However, the lower mean scores and higher standard deviations from faculty responses raise concern, as do the significant differences between individual dental programs and the dental program itself a significant predictor. Further review of programs is needed, and a national set of dental competencies should be considered in this country.
Enhanced mechanical properties for porous ceramics with an in situ formation of anorthite crystals during vitrification
Authors: Zhang Kaijie , Liu Meijuan , Han Zhichao , Sun Haibin , Li Xiaowei , Bai Jiahai , Du Qingyang , Li Chengfeng
Published: December 2022

Porous anorthite ceramics are widely applied as catalysis supports, separation membranes, and thermal insulations at high temperatures. In situ formation of anorthite crystals during vitrification is herein employed to improve mechanical properties of porous anorthite with modulated grain sizes on pore walls. Sintering parameters of shrinkage (5%–30%), open porosity (31.0%–58.3%), density (1.18–1.71 g/cm3), and mass loss (12.20%–18.26%) are estimated to investigate the influences of sintering aids of calcite, fused mullite, and silicon carbide or talcum on the densification processes of porous anorthite. The Kissinger equation is used to determine the activation energy of 783 kJ/mol for the crystallization of anorthite, which is significantly low for the formation of anorthite crystals through surface nucleation mechanism in present flux‐rich melt. In situ crystallization and simultaneous densification under liquid drainages are favored for whiskers‐reinforced mechanism to enhance flexural strengths (6.9–19.4 MPa) for porous anorthite with the porosity of 49.6%–58.3% through the formation of hierarchical nano‐ and microscale structures during vitrification.
Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non‐clear cell renal cell carcinoma: Real‐world data from a Japanese multicenter retrospective study
Authors: Izumi Keita , Inoue Masaharu , Washino Satoshi , Shirotake Suguru , Kagawa Makoto , Takeshita Hideki , Miura Yuji , Hyodo Yoji , Oyama Masafumi , Kawakami Satoru , Miyagawa Tomoaki , Saito Kazutaka , Kageyama Yukio
Published: December 2022

Objectives

Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non‐clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC.

Methods

We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first‐line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression‐free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups.

Results

The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow‐up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment‐related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients.

Conclusions

Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.
Réponses Contractiles Aux Catécholamines des Artères Rénale et Iliaque en Présence d'Halothane Chez le Porc Sensible à l'Hyperthermie Maligne
Authors: Nadeau S. , DeRoth L.
Published: December 2022

Contractile response to catecholamines in the presence of halothane of renal and iliac arterial rings in pigs susceptible to malignant hyperthermia

During halothane induced reaction in pigs susceptible to porcine stress syndrome, and consequently to malignant hyperthermia an unstable blood pressure is characteristic. The objectives of this study were to evaluate the m vitro reactivity of renal and iliac arteries to catecholamines, in the presence of halothane, of pigs susceptible to malignant hyperthermia. Logarithmically increased concentrations of epinephrine and norepinephrine produced vascular contraction of a sigmoid type, in a dose‐dependent fashion. The presence of 5 % halothane moderately inhibited the catecholaminergic response of renal arterial rings of malignant hyperthermia susceptible animals as a non‐specific antagonist.
Enzyme Profile in Blood and Tissues of Chickens Fed Various Levels of Monensin
Authors: Horovitz C.T. , Avidar Y. , Bogin E. , Shlosberg A. , Shkap I. , Weisman Y. , Egyed M.N.
Published: December 2022

The influence of recommended prophylactic doses or overdosages of moiiensin on growth and on enzymatic activities in blood and in various organs of 5 — 8 week old broiler chickens was investigated. Feeding of 300 or 400ppm monensin in the ration caused a reduction of feed consumption, paralysis, a 13—20% mortality and a retardation in body weight gain of the survivors. A tendency to recovery, probably as a result of gradually acquired tolerance, was evident in the second week of monensin feeding. Considerable incre.ise in the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), creatine phosphokinase (CPK) and malic enzyme (ME) occurred in plasma as influenced by toxic levels of monensin. Significant increases in alkaline phosphause (ALP), AST and alanine aminotransferase (ALT) activities were recorded in the liver and to a lesser extent in thigh muscle at 400 ppm monensin, but the activity of cardiac CPK was significantly decreased. Tlie prophylactic dose of 100 ppm monensin affected those enzymes involved in key met.ibolism, such as LDH, MDH and AST, most evidently after 5 days of feeding.
The Effect of a Diet with a High or Low Content of Vitamin E on Different Skeletal Muscles and Myocardium in Pigs
Authors: Jensen M. , Essén‐Gustavsson B. , Hakkarainen J.
Published: December 2022

Two groups of growing pigs were fed a barley‐based diet with a low or high content of vitamin K, Biopsy specimens were taken from different skeletal muscles and from the myocardium and analysed for enzyme activities, fibre type composition and content of vitamin E. The highest vitamin E value and oxidative capacity were observed in the myocardium. The skeletal muscles with the highest oxidative capacity also possessed the greatest capacity for storage of vitamin E. The vastus médius showed the highest percentage of type I and type IIA fibres and the highest content of vitamin E. The superficial portion of the biceps femoris with the lowest percentage of type 1 and type IIA fibres had the lowest content of vitamin E. Histochemical stainings showed that type 1 and IIA fibres contained more lipid and had a greater oxidative capacity than type IIB fibres.

This study shows that the content and storage capacity of vitamin E is related to the oxidative capacity of the mu.scle and the amount of lipid containing type I fibres. Furthermore, vitamin E deficiency may be associated with the occurrence of giant fibres.
LH‐Patterns in Jugular Plasma and Oestradiol‐17ß and Progesterone in Utero‐ovarian and Jugular Plasma of Primiparous Sows around Weaning
Authors: Rojanasthien S.
Published: December 2022

The endocrine responses of six primiparous sows were studied following weaning. Blood samples were obtained from the utero‐ovarian and jugular veins during late lactation and following weaning according to the following schedule: every 15 min for 6h one day before and one day alter weaning for LH analysis and at 3h (9.00 a.m. — 9.00 p.m.) or 8h (7.00 a.m. — 11.00 p.m.) intervals from the day of weaning until oestrus or 24 days after weaning for oestradiol‐17ß and progesterone analyses. Four sows showed oestrus within 108—160 h after weaning, one on day 22 after weaning and one sow did not show oestrus before slaughter (24 days after weaning). LH activity, low during lactation, increased significantly one day after weaning in all sows, with the most evident change being an increased frequency of LH pulses. Increases in oestradiol‐17ß concentrations were detected 24 —36h earlier in the utero‐ovarian vein than in the jugular vein. Tbere were several temporary elevations of oestradiol‐l7ß concentration in the utero‐ovarian vein during the post‐weaning period of the sows with delayed oestrus and post‐weaning anoestrus, suggesting the presence of some ovarian follicle activity. These changes in oestradioI‐17 ß concentrations were not observed in jugular vein blood. These results indicate that the weaning to oestrus interval is related to changes in the LH activity after weaning. The ovaries of the sows with delayed oestrus and post‐weaning anoestrus had some antral follicle development, since they could produce and release oestradiol‐17 ß into the blood circulation. This suggests that insufficiency of the hypothalamo‐hypophysial activity might be the cause of an inability of some sows to re‐establish ovarian activity after weaning.
Ossifikationsvarianten am Gliedmaßenskelett des Hundes
Authors: Mayrhofer Elisabeth
Published: December 2022

Ossification Variants in the Limb Skeleton of the Dog. I. Temporary Centres in Growing Dogs

In growing dogs, especially those of large and giant breeds, secondary centres of ossification can be found near to the joints of the extremities. They may be obligatory or optional. On radiograpiis they appear as small shadows of bone density close to the skeleton, preferably in dogs between 4 and 6 months old. These ossification centres can only be demonstrated for a short period of 2 to 4 weeks. They complete the surfaces of joints (scapula, acetabulum) or can be interpreted as partial ossifications of epi‐ or apophyseal cartilage (distal growth‐plate of humerus, distal apophyseal plate of Tuberositas tibiae). The most frequent localizations are: Tuberculum supraglenoidale, Tuberculum inajus, cranio‐ lateral tuberosity of Olecranon, insertion of the lateral collateral ligament in proximal Radius, Processus styloideus ulnae, Processus styloideus ossis accessorii, Trochanter major. Malleolus medialis and lateralis. After fusion, the linked bone gets its definitive shape. These physiological bone shadows can only be diagnosed correctly by relating them to the age of the dog and by comparing them with findings on corresponding radiographs of the opposite extremity.
Suppression of Mitogenic Activity of T Lymphocytes by Subtoxic Concentration of Ammonia in Blood*
Authors: Kiuciński W. , Ostaszewski P. , Winnicka A. , Targowski S. , Szeleszczuk B. , Miernik‐Degórska E.
Published: December 2022

The effect of subtoxic ammonia concentrations in blood on T lymphocyte activity was studied in 8 Merino sheep. In 4 sheep hyperammonemia was produced by continuous three‐day infusion of an ammonium acetate solution into the right jugular vein. Four control sheep received a similar infusion of 0,9% sodium chloride.

Blood samples were obtained from the left jugular vein at 24 hours and immediately before the infusion, and then 24, 48 and 72 hours after the beginning of infusion, and again 96 hours after the beginning of the infusion. The .activity of T lymphocytes was determined by the blastic transformation test.

A significant rise in blood ammonia concentration occurred 24 and 48 hours after the beginning of the infusion.

A parallel fall in ‘H‐thymidine incorporation by lymphocytes was observed in PHA‐ and in Con A‐stimulated T lymphocytes 24, 48 and 72 hours after the beginning of the infusion. The results suggest that increased blood ammonia concentration causes damage to the cell‐mediated immunity mechanisms which may increase susceptibility to infectious agents.
Perinatal Blood Gas and Acid‐Base Status of Caesarean‐derived Calves
Authors: Szenci O. , Taverne M. A. M.
Published: December 2022

Blood gas and acid‐base status of 44 Caesarean‐derived calves (all in anterior presentation) were determined in blood samples obtained before the onset of extraction and after it. Calves were assigned to one of three groups according to their blood pH value: group 1 = normal, pH above 7.2; group 2 = slightly acidotic, pH 7.2 to 7.0; group 3 = severely acidotic, pH below 7.0. Before the onset of extraction (i.e. 4 to 5 hours after the appearance and spontaneous rupture of foetal membranes), 28 calves (63.6%) had normal acid‐base values, 10 (22.7%) had slight acidosis, and 6 (13.7%) had severe acidosis. Vigorous leg movements during extraction direct attention to the occurrence of severe acidosis. At birth the three groups of calves showed the following distribution: 22 (50%) were normal, 15 (34.1 %) had slight acidosis, and 7 (15.9%) had severe acidosis. The acid‐base balance of calves during extraction was mainly shifted to respiratory acidosis. During the first ten minutes after birth a tendency towards metabolic acidosis was observed. After ten minutes spontaneous normalization of respiratory and metabolic acidosis took place but the significant differences among the groups remained unchanged until 60 minutes after birth.
The price of reputation: Executive compensation of sin companies
Authors: Chen Sheng‐Syan , Shen Carl Hsin‐han , Wang Yanzhi
Published: December 2022

This study examines how and why managers receive pay premiums when vulnerable to social reputation loss. We define sin companies as those operating in the alcohol, gambling and tobacco industries. We show that company managers receive a higher asymmetric pay‐for‐performance sensitivity in their pay in addition to receiving higher total compensation. In other words, their pay increases with firm performance at a faster rate than that of their non‐sin company peers. This finding is consistent with our prediction that sin companies provide greater rewards to their managers upon satisfactory performance, generating a pay premium. We propose two explanations for the reputation pay premium associated with sin‐industry managers: the limited future career opportunities and the difficulty of reconciling managers’ self‐identity with the employer's social identity. We find stronger support for the latter explanation. The sin‐industry pay premium is larger when managers have pro‐social and religious tendencies. However, we do not find a smaller pay premium when managers are close to their retirement. Since the career concern should be reduced for managers who are near retirement, this finding is inconsistent with the career opportunity explanation. Overall, our findings are consistent with the notion that managers associate their self‐image with employers’ social identities.
Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension
Authors: Avorgbedor Forgive , Blumenthal James A. , Hinderliter Alan , Ingle Krista , Lin Pao‐Hwa , Craighead Linda , Tyson Crystal , Kraus William , Sherwood Andrew , Smith Patrick J.
Published: December 2022

Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro‐inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C‐reactive protein (hsCRP) and were subsequently randomized to an intensive 4‐month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre‐intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
Circular RNA CircSLC8A1 contributes to osteogenic differentiation in hBMSCs via CircSLC8A1/miR‐144‐3p/RUNX1 in periprosthetic osteolysis
Authors: Yang Boning , Qin Yu , Zhang Ao , Wang Penghao , Jiang Hua , Shi Yunyi , You Guanchao , Shen Dianlin , Ni Shenghui , Guo Lei , Liu Ying
Published: December 2022

Circular RNAs (circRNAs) are often found in eukaryocyte and have a role in the pathogenesis of a variety of human disorders. Our related research has shown the differential expression of circRNAs in periprosthetic osteolysis (PPOL). However, the involvement of circRNAs in the exact process is yet unknown. CircSLC8A1 expression was evaluated in clinical samples and human bone marrow mesenchymal stem cells (hBMSCs) in this investigation using quantitative real‐time PCR. In vitro and in vivo studies were conducted to explicate its functional role and pathway. We demonstrated CircSLC8A1 is involved in PPOL using gain‐ and loss‐of‐function methods. The association of CircSLC8A1 and miR‐144‐3p, along with miR‐144‐3p and RUNX1, was predicted using bioinformatics. RNA pull‐down and luciferase assays confirmed it. The impact of CircSLC8A1 in the PPOL‐mouse model was also investigated using adeno‐associated virus. CircSLC8A1 was found to be downregulated in PPOL patients' periprosthetic tissues. Overexpression of CircSLC8A1 promoted osteogenic differentiation (OD) and inhibited apoptosis of hBMSCs in vitro. The osteogenic markers of RUNX1, osteopontin (OPN) and osteocalcin (OCN) were significantly upregulated in hBMSCs after miR‐144‐3p inhibitor was transferred. Mechanistic analysis demonstrated that CircSLC8A1 directly bound to miR‐144‐3p and participated in PPOL through the miR‐144‐3p/RUNX1 pathway in hBMSCs. Micro‐CT and quantitative analysis showed that CircSLC8A1 markedly inhibited PPOL, and osteogenic markers (RUNX1, OPN and OCN) were significantly increased (P<0.05) in the mice model. Our findings prove that CircSLC8A1 exerted a regulatory role in promoting osteogenic differentiation in hBMSCs, and CircSLC8A1/miR‐144‐3p/RUNX1 pathway may provide a potential target for prevention of PPOL.
Glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 secretion in humans: Characteristics and regulation
Authors: Alsalim Wathik , Lindgren Ola , Ahrén Bo
Published: December 2022

Aims/Introduction

Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are important incretin hormones. They are released from the gut after meal ingestion and potentiate glucose‐stimulated insulin secretion. Their release after meal ingestion and oral glucose are well established and have been characterized previously. During recent years, knowledge of other regulatory aspects that potentially may affect GIP and GLP‐1 secretion after meal ingestion have also begun to emerge. Here, the results of human studies on these novel aspects of meal‐ and nutrient‐stimulated incretin hormone secretion are reviewed.

Materials and Methods

The human literature was revisited by identifying articles in PubMed using key words GIP, GLP‐1, secretion, meal, and nutrients.

Results

The results show that all macronutrients individually stimulate GIP and GLP‐1 secretion. However, there was no synergistic action when given in combination. A pre‐load 30 min before a meal augments the GIP and GLP‐1 response. GIP and GLP‐1 secretion have a diurnal variation with a higher response to an identical meal in the morning than in the afternoon. There is no difference in GIP and GLP‐1 secretion whether a meal is ingested slowly or rapidly. GIP and GLP‐1 secretion after dinner are the same whether or not breakfast and lunch have been ingested. The temperature of the food may be of importance for the incretin hormone response.

Conclusions

These novel findings have increased our knowledge on the regulation of the complexity of the incretin system and are also important knowledge when designing future studies.
Effects of dietary supplementation with bioactive peptides derived from rapeseed protein on the growth performance, serum biochemistry and faecal micro‐organism composition of weaned piglets
Authors: Zhong Xiaoxia , Lin Peiwen , Yao Yanchu , Liu Zhiyun , Zhou Xiaorong , Guan Xiaofeng , Huang Jinxiu
Published: December 2022

The present study investigated the effects of supplementing bioactive peptides derived from rapeseed protein (rapeseed peptide, Rsp) on the growth performance, serum biochemistry and faecal micro‐organism composition of weaned piglets. Sixty Duroc × Landrace × Yorkshire weaned piglets of similar weights were randomly divided into three groups. The control group (NC) was fed a basal diet, and the two treatment groups, Rsp‐1 and Rsp‐2, were fed a basal diet supplemented with 1% or 2% Rsp, respectively, for 28 days. Each treatment consisted of five replicates with four piglets per replicate. The results showed that Rsp treatment significantly improved the average daily gain and had a better feed‐to‐gain ratio (p < 0.05). The diarrhoea incidence and indices of Rsp‐1 and Rsp‐2 groups were significantly lower than the NC group (p < 0.05), and the effect of Rsp‐2 on reducing the incidence of diarrhoea was significantly higher than that of Rsp‐1 (p < 0.05). The serum albumin, serum immunoglobulin A and catalase levels of the Rsp‐1 and Rsp‐2 groups were significantly better than the NC group (p < 0.05). Additionally, Rsp treatment significantly gained the relative abundance of faecal Lactobacillaceae and decreased the relative abundance of faecal Eubacterium_coprostanoligenes_group, Treponema and Coprococcus (p < 0.05). In summary, Rsp supplementation improved the growth performance, ameliorated the diarrhoea, enhanced the immune and antioxidant functions and changed the composition of faecal micro‐organisms in piglets. These findings indicate that Rsp positively affected the health of weaned piglets.
Cold stress‐induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of aM3‐muscarinic antagonist and a β3‐adrenergic agonist
Authors: Hara Hiroaki , Imamura Tetsuya , Suzuki Ataru , Ueno Manabu , Minagawa Tomonori , Ogawa Teruyuki , Ishizuka Osamu
Published: December 2022

Objectives

Goto‐Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3‐muscarinic receptor antagonist and a β3‐adrenergic receptor agonist.

Methods

Ten‐week‐old female GK rats were fed a high‐fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle,the M3‐muscarinic receptor antagonist solifenacin, the β3‐adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3‐muscarinic and β3‐adrenergic receptors were investigated.

Results

After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle‐, solifenacin‐, or mirabegron‐treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3‐muscarinic and β3‐adrenergic receptors were detected, the expression of M3‐muscarinic receptor mRNA was significantly higher than that of β3‐adrenergic receptor mRNA.

Conclusions

The cold stress‐induced bladder overactivity was not improved by either the M3‐muscarinic receptor antagonist or the β3‐adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3‐muscarinic antagonists and β3‐adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.
Channeling Voices to Improve L2 English Intelligibility
Authors: LASCOTTE DARREN K. , TARONE ELAINE
Published: December 2022

In commercial materials for the teaching of second language (L2) pronunciation, common bottom‐up approaches segment phonology into a series of discrete and decontextualized linguistic components with rules that students are encouraged to internalize. Such approaches seem out of step with recent second language acquisition (SLA) theory and research that emphasize the central influence of social context, interlocutor, empathy, and nonverbal elements on the meaningful use of L2 forms. Research showing that these factors profoundly influence the pronunciation of an L2 in social discourse suggests a more top‐down, holistic pedagogy to better harness the agentive energy of motivated and goal‐oriented L2 learners. Drawing on findings in interlanguage phonology and Bakhtinian sociocultural theory, this article documents ways that 7 adult L2 learners in an intensive English program improved their English intelligibility, while some of them also improved their delivery, as they all mirrored and subsequently channeled the voices of model speakers in rehearsed oral presentations over the course of a short 7‐week pedagogical treatment. The findings of this study support the view that the construct of voice and the influence of social contextual factors in SLA are critical in shaping interlanguage phonology and raise a number of important pedagogical implications for addressing learning outcomes in L2 pronunciation.
Hyperviscosity syndrome complicating immunoglobulin G myeloma—Cognisance of early plasmapheresis is crucial
Authors: Vivek Sood , Kundan Mishra , Rajat Bahl , Gaurav Singhal , Manu Dogra , Suman Pramanik , Singh Vishal
Published: December 2022

Hyperviscosity syndrome (HVS) is an infrequent but life‐threatening complication of multiple myeloma (MM) and classically presents with the triad of mucosal bleed, neurological, and visual disturbances. HVS is typically associated with immunoglobulin M (IgM) MM and very rarely may complicate immunoglobulin G (IgG) MM. Even suspicion of HVS necessitates therapy based on clinical severity rather than the calculated degree of viscosity. While plasmapheresis promptly decreases serum viscosity by 30% to 50%, early initiation of anti‐myeloma therapy is crucial to prevent rebound phenomena. In this context, we report a case of IgG MM, which despite being complicated by HVS had gratifying outcome attributable to early clinical suspicion and consequent prompt therapeutic intervention.
Longitudinal trajectories of maternal parenting stress in Korean families: Children's executive function and school adjustment
Authors: Park SuJung , Oh Wonjung , Kim Yunhee , Kim Hyoun K. , Mastergeorge Ann M.
Published: December 2022

A majority of mothers experience parenting stress in daily life; however high levels of maternal stress have been recognized as a risk factor for children's developmental outcomes. We examined trajectories of maternal parenting stress across childhood, and their longitudinal relations to children's executive function and school adjustment. Data were drawn from the Panel Study on Korean Children (PSKC), which included 1754 mothers across five waves measured at children ages 3, 4, 5, 6, and 7 (boys = 51%). Results of Latent Growth Curve Modeling (LGCM) revealed that, on average, maternal parenting stress decreased over time, but there were significant variabilities in the initial levels at age 3 and changes across early through middle childhood. High initial levels of stress and an increase in maternal parenting stress over time were associated with lower executive function at age 7 in planning‐organizing and attention concentration. An increment in maternal parenting stress over time was related to poorer school adjustment at age 7, measured by classroom behavior, positive approach to learning, and child‐peer and child‐teacher relationships. These findings support cultural commonality and may contribute to the instantiation of culturally universal, early preventions and interventions to support mothers’ mental health. Efforts aimed at reducing maternal parenting stress early in development may promote better long‐term developmental outcomes, including executive functioning and school adjustment of children in their first year of elementary school.
Evaluation of a new connected portable camera for the analysis of skin microrelief and the assessment of the effect of skin moisturisers
Authors: Gougeon Sarah , Hernandez Elsa , Chevrot Nathalie , Vergne Thibault , Cherel Marie , Prestat‐Marquis Elodie , Jomier Matthieu , Burty‐Valin Elodie
Published: December 2022

Background

Silicone replicas and non‐contact methods are effective methods to analyse the micrometric scale of the skin microrelief. Yet, they imply data capture in research facilities. The capabilities of a new connected portable camera were evaluated to analyse microrelief under nomadic conditions, also studying the effect of moisturisers.

Materials and methods

3D depth maps were constructed using shape‐from‐shading algorithms. Roughness heterogeneity (Spa) was computed, and skin profiles were extracted to calculate roughness amplitude (Ra, Rq), as well as furrows/plateaus characteristics. Validation of the connected camera was performed on tanned cowhide leather and on the inner forearm skin of a single subject. The forearms of 18 subjects (23–60 years old) were also evaluated. While living their regular life, they self‐performed triplicate acquisitions at various times. The effects of a placebo and of cream containing moisturisers—saccharide isomerate, urea or xylitylglucoside–anhydroxylitol–xylitol—were investigated, using untreated control skin as a reference.

Results

Validation of the device on leather and forearm skin shows high repeatability. The 18 subjects show the known correlation between age and changes in microrelief. While testing formulas, 8 h after a single application, all decreased Spa (−1.6/−2.1 folds). Only saccharide isomerate and xylitylglucoside–anhydroxylitol–xylitol decreased Ra (−2.4/−2.8 folds). The sectional area of plateaus was reduced from −1.5 (urea) to −2.1 folds (xylitylglucoside–anhydroxylitol–xylitol). The height of plateaus is also decreased by all moisturisers, from −1.5 (urea) to −2.1 folds (xylitylglucoside–anhydroxylitol–xylitol).

Conclusion

This novel camera device enables microrelief analysis under nomadic conditions, allowing monitoring its changes along the day and upon moisturisers’ application.
Intramuscle Synergies: Their Place in the Neural Control Hierarchy
Authors: Latash Mark L. , Madarshahian Shirin , Ricotta Joseph M.
Published: December 2022

We accept a definition of synergy introduced by Nikolai Bernstein and develop it for various actions, from those involving the whole body to those involving a single muscle. Furthermore, we use two major theoretical developments in the field of motor control—the idea of hierarchical control with spatial referent coordinates and the uncontrolled manifold hypothesis—to discuss recent studies of synergies within spaces of individual motor units (MUs) recorded within a single muscle. During the accurate finger force production tasks, MUs within hand extrinsic muscles form robust groups, with parallel scaling of the firing frequencies. The loading factors at individual MUs within each of the two main groups link them to the reciprocal and coactivation commands. Furthermore, groups are recruited in a task-specific way with gains that covary to stabilize muscle force. Such force-stabilizing synergies are seen in MUs recorded in the agonist and antagonist muscles but not in the spaces of MUs combined over the two muscles. These observations reflect inherent trade-offs between synergies at different levels of a control hierarchy. MU-based synergies do not show effects of hand dominance, whereas such effects are seen in multifinger synergies. Involuntary, reflex-based, force changes are stabilized by intramuscle synergies but not by multifinger synergies. These observations suggest that multifinger (multimuscle synergies) are based primarily on supraspinal circuitry, whereas intramuscle synergies reflect spinal circuitry. Studies of intra- and multimuscle synergies promise a powerful tool for exploring changes in spinal and supraspinal circuitry across patient populations.
Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells
Authors: McCool Elijah N. , Xu Tian , Chen Wenrong , Beller Nicole C. , Nolan Scott M. , Hummon Amanda B. , Liu Xiaowen , Sun Liangliang
Published: December 2022

Understanding cancer metastasis at the proteoform level is crucial for discovering previously unknown protein biomarkers for cancer diagnosis and drug development. We present the first top-down proteomics (TDP) study of a pair of isogenic human nonmetastatic and metastatic colorectal cancer (CRC) cell lines (SW480 and SW620). We identified 23,622 proteoforms of 2332 proteins from the two cell lines, representing nearly fivefold improvement in the number of proteoform identifications (IDs) compared to previous TDP datasets of human cancer cells. We revealed substantial differences between the SW480 and SW620 cell lines regarding proteoform and single amino acid variant (SAAV) profiles. Quantitative TDP unveiled differentially expressed proteoforms between the two cell lines, and the corresponding genes had diversified functions and were closely related to cancer. Our study represents a pivotal advance in TDP toward the characterization of human proteome in a proteoform-specific manner, which will transform basic and translational biomedical research.
Use of intercellular proximity labeling to quantify and decipher cell-cell interactions directed by diversified molecular pairs
Authors: Qiu Shuang , Zhao Zihan , Wu Mengyao , Xue Qi , Yang Yang , Ouyang Shian , Li Wannan , Zhong Lingyu , Wang Wenjian , Yang Rong , Wu Peng , Li Jie P.
Published: December 2022

FucoID is an intercellular proximity labeling technique for studying cell-cell interactions (CCIs) via fucosyltransferase (FT)–meditated fucosyl-biotinylation, which has been applied to probe antigen-specific dendritic cell (DC)–T cell interactions. In this system, bait cells of interest with cell surface–anchored FT are used to capture the interacting prey cells by transferring a biotin-modified substrate to prey cells. Here, we leveraged FucoID to study CCIs directed by different molecular pairs, e.g., programmed cell death protein-1(PD-1)/programmed cell death protein-ligand-1 (PD-L1), and identify unknown or little studied CCIs, e.g., the interaction of DCs and B cells. To expand the application of FucoID to complex systems, we also synthesized site-specific antibody-based FT conjugate, which substantially improves the ability of FucoID to probe molecular signatures of specific CCI when cells of interest (bait cells) cannot be purified, e.g., in clinical samples. Collectively, these studies demonstrate the general applicability of FucoID to study unknown CCIs in complex systems at a molecular resolution.