bluuebunny/crossref_metadata_2025 huggingface dataset:
The spliceophilin CYP18‐2 is mainly involved in the splicing of retained introns under heat stress inArabidopsis
Authors: Lee Areum , Park Hyun Ji , Jo Seung Hee , Jung Haemyeong , Kim Hyun‐Soon , Lee Hyo‐Jun , Kim Youn‐Sung , Jung Choonkyun , Cho Hye Sun
Published: January 2023

Peptidyl‐prolyl isomerase‐like 1 (PPIL1) is associated with the human spliceosome complex. However, its function in pre‐mRNA splicing remains unclear. In this study, we show thatArabidopsis thalianaCYCLOPHILIN 18‐2 (AtCYP18‐2), a PPIL1 homolog, plays an essential role in heat tolerance by regulating pre‐mRNA splicing. Under heat stress conditions,AtCYP18‐2expression was upregulated in mature plants and GFP‐tagged AtCYP18‐2 redistributed to nuclear and cytoplasmic puncta. We determined that AtCYP18‐2 interacts with several spliceosome complex BACTcomponents in nuclear puncta and is primarily associated with the small nuclear RNAsU5andU6in response to heat stress. TheAtCYP18‐2loss‐of‐function allelecyp18‐2engineered by CRISPR/Cas9‐mediated gene editing exhibited a hypersensitive phenotype to heat stress relative to the wild type. Moreover, global transcriptome profiling showed that thecyp18‐2mutation affects alternative splicing of heat stress–responsive genes under heat stress conditions, particularly intron retention (IR). The abundance of most intron‐containing transcripts of a subset of genes essential for thermotolerance decreased incyp18‐2compared to the wild type. Furthermore, the intron‐containing transcripts of two heat stress‐related genes,HEAT SHOCK PROTEIN 101(HSP101) andHEAT SHOCK FACTOR A2(HSFA2), produced functional proteins. HSP101‐IR‐GFP localization was responsive to heat stress, and HSFA2‐III‐IR interacted with HSF1 and HSP90.1 in plant cells. Our findings reveal that CYP18‐2 functions as a splicing factor within the BACTspliceosome complex and is crucial for ensuring the production of adequate levels of alternatively spliced transcripts to enhance thermotolerance.
A high‐confidence Physcomitrium patens plasmodesmata proteome by iterative scoring and validation reveals diversification of cell wall proteins during evolution
Authors: Gombos Sven , Miras Manuel , Howe Vicky , Xi Lin , Pottier Mathieu , Kazemein Jasemi Neda S. , Schladt Moritz , Ejike J. Obinna , Neumann Ulla , Hänsch Sebastian , Kuttig Franziska , Zhang Zhaoxia , Dickmanns Marcel , Xu Peng , Stefan Thorsten , Baumeister Wolfgang , Frommer Wolf B. , Simon Rüdiger , Schulze Waltraud X.
Published: January 2023

Plasmodesmata (PD) facilitate movement of molecules between plant cells. Regulation of this movement is still not understood. Plasmodesmata are hard to study, being deeply embedded within cell walls and incorporating several membrane types. Thus, structure and protein composition of PD remain enigmatic. Previous studies of PD protein composition identified protein lists with few validations, making functional conclusions difficult.

We developed a PD scoring approach in iteration with large‐scale systematic localization, defining a high‐confidence PD proteome of Physcomitrium patens (HC300). HC300, together with bona fide PD proteins from literature, were placed in Pddb. About 65% of proteins in HC300 were not previously PD‐localized.

Callose‐degrading glycolyl hydrolase family 17 (GHL17) is an abundant protein family with representatives across evolutionary scale. Among GHL17s, we exclusively found members of one phylogenetic clade with PD localization and orthologs occur only in species with developed PD. Phylogenetic comparison was expanded to xyloglucan endotransglucosylases/hydrolases and Exordium‐like proteins, which also diversified into PD‐localized and non‐PD‐localized members on distinct phylogenetic clades.

Our high‐confidence PD proteome HC300 provides insights into diversification of large protein families. Iterative and systematic large‐scale localization across plant species strengthens the reliability of HC300 as basis for exploring structure, function, and evolution of this important organelle.
Influence of location, season and time of day on the spectral composition of ambient light: Investigation for application in myopia
Authors: Dhakal Rohit , Huntjens Byki , Shah Rakhee , Lawrenson John G. , Verkicharla Pavan K.
Published: January 2023

Purpose

Given the possible role of spectral composition of light and myopia, this study aimed at investigating the variation in the spectral composition of ambient light in different (a) outdoor/indoor locations, (b) time of a day and (c) seasons.

Methods

The spectral power distribution (SPD), categorised into short (380–500 nm), middle (505–565 nm) and long wavelengths (625–780 nm), was recorded using a handheld spectrometer at three outdoor locations (‘open playground’, ‘under shade of tree’ and ‘canopy’) and three indoor locations (‘room with multiple windows’, ‘closed room’ and ‘closed corridor’). Readings were taken at five different time points (3‐h intervals between 6:30 and 18:00 hours) on two days, each during the summer and monsoon seasons.

Results

The overall median SPD (IQR [25th‐75th percentile] W/nm/m2) across the three outdoor locations (0.11 [0.09, 0.12]) was 157 times higher than that of the indoor locations (0.0007 [0.0001, 0.001]). Considerable locational, diurnal and seasonal variation was observed in the distribution of the median SPD value, with the highest value being recorded in the ‘open playground’ (0.27 [0.21, 0.28]) followed by ‘under shade of tree’ (0.083 [0.074, 0.09]), ‘canopy’ (0.014 [0.012, 0.015]) and ‘room with multiple windows’ (0.023 [0.015, 0.028]). The relative percentage composition of short, middle and long wavelengths was similar in both the outdoor and indoor locations, with the proportion of middle wavelengths significantly higher (p < 0.01) than short and long wavelengths in all the locations, except ‘canopy’.

Conclusion

Irrespective of variation in SPD values with location, time, day and season, outdoor locations always exhibited significantly higher spectral power than indoor locations. The relative percentage composition of short, middle and long wavelengths of light was similar across all locations. These findings establish a foundation for future research to understand the relationship between spectral power and the development of myopia.
Dynamics of mother‐infant parasympathetic regulation during face‐to‐face interaction: The role of maternal emotion dysregulation
Authors: Gao Mengyu (Miranda) , Vlisides‐Henry Robert D. , Kaliush Parisa R. , Thomas Leah , Butner Jonathan , Raby K. Lee , Conradt Elisabeth , Crowell Sheila E.
Published: January 2023

The dynamics of parent‐infant physiology are essential for understanding how biological substrates of emotion regulation are organized during infancy. Although parent‐infant physiological processes are dyadic in nature, research is limited in understanding how one person's physiological responses predict one's own and as well as the other person's responses in the subsequent moment. In this study, we examined mother‐infant respiratory sinus arrhythmia (RSA) dynamics during the Still‐Face Paradigm (SFP) among 106 mothers (Mage = 29.54) and their 7‐month‐old infants (55 males). Given mothers' role in shaping dyadic interactions with their infant, we also tested how mothers' self‐reported emotion dysregulation (measured via the Difficulties in Emotion Regulation Scale) associated with these dynamics. Results showed that both mothers' and infants' RSA tended to return to their respective homeostatic points (i.e., exhibited return strength) during each SFP episode, indicating stability in RSA for mother‐infant dyads. Significant shifts in mother and infant RSA return strength were observed across SFP episodes, highlighting the role of contextual demands on each individual's physiological dynamics. Mother‐infant RSA dynamics varied as a function of maternal self‐reported emotion dysregulation. Specifically, RSA levels of infants with more dysregulated mothers had a weaker tendency to return to homeostasis during the Reunion episode and were less affected by their mothers' RSA during the Still‐Face and Reunion episodes of the SFP, suggesting a less effective coregulatory influence. Our findings have implications for the intergenerational transmission of emotion dysregulation via mother‐infant physiological dynamics.
Sentinel lymph node mapping with computed tomography lymphography for mast cell tumours and a comparison between regional and sentinel lymph node histological status: Sixty‐two cases
Authors: Ferraris Erica Ilaria , Olimpo Matteo , Giacobino Davide , Manassero Luca , Iussich Selina , Lardone Elena , Camerino Mariateresa , Buracco Paolo , Morello Emanuela Maria
Published: January 2023

It is known that the regional lymph node (RLN) may not correspond to the sentinel lymph node (SLN) (the first lymph node draining the tumour), and many diagnostic techniques have recently been aimed at its detection. Although lymphoscintigraphy is the gold standard in both human and veterinary medicine for SLN mapping, it is relatively unavailable in veterinary medicine due to costs and difficult management of the radiotracer. This prospective study evaluated, as a first aim, the feasibility and sensitivity of the computed tomography lymphography (CTL) in detecting the SLN in 62 mast cell tumours (MCTs). The second aim was to evaluate the accuracy of the CTL in identifying the most representative lymph node of the patient's lymphatic status; the histological status of the SNL was compared with that of the RLN, to see in how many cases the patient's stage would have changed according to the RLN. When the RLN turned out to be also the SLN it was decided to excise, as a control LN, the one localised in the neighbourhood of the MCT (neighbouring lymph node; NLN). The detection rate was 90%, with failure of SLN identification in six cases. In 18 (32%) of 56 MCTs with a diagnostic CTL, the SLN did not correspond to the RLN. Forty‐five MCTs were surgically removed, together with their corresponding SLN and RLN/NLN. Since the clinical stage of the patient would have changed in only 7% of cases, CTL is a reliable method of detecting the SLN and, for staging purposes, there is no need to remove other LNs.
LAMP-enabled diagnosis of Kaposi’s sarcoma for sub-Saharan Africa
Authors: McCloskey Duncan , Semeere Aggrey , Ayanga Racheal , Laker-Oketta Miriam , Lukande Robert , Semakadde Matthew , Kanyesigye Micheal , Wenger Megan , LeBoit Philip , McCalmont Timothy , Maurer Toby , Gardner Andrea , Boza Juan , Cesarman Ethel , Martin Jeffrey , Erickson David
Published: January 2023

Kaposi’s sarcoma (KS) is an endothelial cancer caused by the Kaposi’s sarcoma-associated herpesvirus (KSHV) and is one of the most common cancers in sub-Saharan Africa. In limited-resource settings, traditional pathology infrastructure is often insufficient for timely diagnosis, leading to frequent diagnoses at advanced-stage disease where survival is poor. In this study, we investigate molecular diagnosis of KS performed in a point-of-care device to circumvent the limited infrastructure for traditional diagnosis. Using 506 mucocutaneous biopsies collected from patients at three HIV clinics in Uganda, we achieved 97% sensitivity, 92% specificity, and 96% accuracy compared to gold standard U.S.-based pathology. The results presented in this manuscript show that LAMP-based quantification of KSHV DNA extracted from KS-suspected biopsies has the potential to serve as a successful diagnostic for the disease and that diagnosis may be accurately achieved using a point-of-care device, reducing the barriers to obtaining KS diagnosis while increasing diagnostic accuracy.
Enantio- and
Z
-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center
Authors: Ge Luo , Sinnema Esther G. , Pérez Juana M. , Postolache Roxana , Castiñeira Reis Marta , Harutyunyan Syuzanna R.
Published: January 2023

Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined
E
-olefines, their thermodynamically less stable
Z
counterparts are substantially more demanding, while access to those bearing an allylic stereocenter with an adjacent reactive functionality remains unsolved altogether. Even the classic Wittig reaction, arguably the most versatile and widely used approach to construct
Z
-alkenes, falls short for the synthesis of these particularly challenging yet highly useful structural motives. Here, we report a general methodology for
Z
-selective synthesis of functionalized chiral alkenes that establishes readily available alkene-derived phosphines as an alternative to alkylating reagents in Wittig olefination, thus offering previously unidentified retrosynthetic disconnections for the formation of functionalized disubstituted alkenes. We demonstrate the potential of this method by structural diversification of several bioactive molecules.
Supplemental Material: Disparate crustal thicknesses beneath oceanic transform faults and adjacent fracture zones revealed by gravity anomalies
Authors: Guo Zhikui , Rüpke Lars Helmuth , al. et
Published: January 2023

Details on the geodynamic model, thermal correction, and additional results of all 11 transform faults. 
Aging is a Side Effect of the Ontogenesis Program of Multicellular Organisms
Authors: Salnikov Lev
Published: January 2023

The review presents a brief outline of the current state of the main theoretical approaches to the aging problem. The works of authors, supporting the theory of “accumulation of errors” and theories stating the presence of a hypothetical “aging program” in all multicellular organisms are reviewed. The role of apoptosis and its connection with phenoptosis, as well as the theory of “hyperfunction” are analyzed. Our own approach to this problem is presented, in which aging is explained by the redistribution of limited resources between the two main aims of the organism: its self-sufficiency, based on the function of the housekeeping genes (HG) group, and functional specialization, provided by the integrative genes (IntG) group. Agreeing with the inseparable connection between aging and the ontogenesis program, the main role in the aging mechanisms is assigned to the redistribution of resources from the HG self-sufficiency genes to the IntGs necessary for the operation of all specialized functions of the organism as a whole. The growing imbalance between HGs and IntGs with age, suggests that switching of cellular resources in favor of IntGs is a side effect of ontogenesis program implementation and the main reason for aging, inherent in the nature of genome functioning under conditions of highly integrated multicellularity. The hypothesis of functional subdivision of the genome also points to the leading role of slow-dividing and postmitotic cells, as the most sensitive to reduction of repair levels, for triggering and realization of the aging process.
General Lebesgue integral inequalities of Jensen and Ostrowski type and applications
Authors: Saraswat Ram Naresh , Tak Ajay
Published: January 2023

Jensen-Ostrowski-type inequalities for general Lebesgue integral are discussed. Here, we derive information inequalities for Lipschitzian derivatives by using new [Formula: see text]-divergence measure which will be useful in Information Theory. In this way, we establish some particular cases of these information inequalities. We also obtain information inequalities for general Lebesgue integral of differentiable functions whose derivatives in absolute value are [Formula: see text]-convex and its particular instances are established.
Evaluation of the Role of Soybean Lecithin, Egg Yolk Lecithin, and Krill Oil in Promoting Ovarian Development in the Female Redclaw Crayfish Cherax quadricarinatus
Authors: Xu Chang , Yang Xiaolong , Liang Zhenye , Jiang Zongzheng , Chen Hu , Han Fenglu , Jia Yongyi , Li Erchao
Published: January 2023

The optimal supplementation of lipid nutrients in the diet showed crucial physiological functions in gonadal development and maturation in adult female aquatic animals. Four isonitrogenous and isolipidic diets with no extra lecithin supplementation (control), 2% soybean lecithin (SL), egg yolk lecithin (EL), or krill oil (KO) supplementation were formulated for Cherax quadricarinatus (

72.32
±
3.58
 
g

). Ovary development and physiological characteristics of crayfish were evaluated after a 10-week feeding trial. The results indicated that SL, EL, or KO supplementation all significantly increased the gonadosomatic index, especially in the KO group. Crayfish fed the diet with SL showed the highest hepatosomatic index compared with those fed the other experimental diets. KO was more efficient than SL and EL in promoting triacylglycerol and cholesterol deposition in the ovary and hepatopancreas but also showed the lowest concentration of low-density lipoprotein cholesterol in the serum. KO significantly increased yolk granule deposition and accelerated oocyte maturation than other experimental groups. Furthermore, dietary phospholipids significantly enhanced the gonad-stimulating hormone concentration in the ovary and reduced the secretion of gonad-inhibiting hormones in the eyestalk. KO supplementation also significantly improved organic antioxidant capacity. From the ovarian lipidomics results, phosphatidylcholine and phosphatidylethanolamine are two main glycerophospholipids that respond to different dietary phospholipids. Polyunsaturated fatty acids (especially C18:2n-6, C18:3n-3, C20:4n-6, C20:5n-3, and C22:6n-3) were pivotal participants during ovarian development of crayfish regardless of lipid type. Combined with the ovarian transcriptome, the best positive function of KO was due to activated steroid hormone biosynthesis, sphingolipid signaling, retinol metabolism, lipolysis, starch and sucrose metabolism, vitamin digestion and absorption, and pancreatic secretion. As a consequence, dietary supplementation with SL, EL, or KO all improved the ovarian development quality of C. quadricarinatus, especially KO, which was the optimum choice for promoting ovary development in adult female C. quadricarinatus.
Royal Jelly Increases Hematopoietic Stem Cells in Peripheral Blood: A Double‐Blind, Placebo‐Controlled, Randomized Trial in Healthy Subjects
Authors: Okamoto Hideto , Ohkuma Akio , Kawaguchi Mitsuhiko , Shigematsu Norihiro , Okumura Nobuaki
Published: January 2023

Objectives. Royal jelly (RJ), produced by honeybees, influences stem cell functions, such as pluripotency maintenance of mouse embryonic stem cells and prevention of aging‐related muscle stem cell functional deterioration. Thus, we hypothesized that RJ administration has various health‐promoting effects based on stem cells. However, its effects are unknown in humans. In this study, we have attempted for the first time to clarify whether the administration of RJ in humans affects stem cells. Materials and Methods. This randomized, double‐blind, placebo‐controlled study was performed on healthy subjects (n = 90) who received protease‐treated RJ at a dose of 1200 mg/day or placebo daily for four weeks. Also, the participants with a low number of hematopoietic stem cells (HSCs) in peripheral blood were preferentially selected. HSC counts, endothelial progenitor cell (EPC) counts, blood cell counts in peripheral blood, cytokines in serum, and physical conditions were evaluated. Results and Conclusion. Eligible data from 86 subjects (placebo: 42, RJ: 44) who completed the study were analyzed. There were no significant differences between the two groups regarding the changes in peripheral HSC count (p = 0.103), while diastolic blood pressure showed a significant improvement in the RJ group compared to that in the placebo group (p = 0.032). The subgroup analysis excluded 14 subjects who complained of cold symptoms at baseline or within five days of the four‐week study. The changes in the HSC populations were significantly higher in the RJ group than those in the placebo group (p = 0.042). No adverse effects were observed in any of the groups. These results suggest that RJ administration affected the peripheral HSC count and may influence stem cell functions. Further research is needed to reveal the various health‐promoting benefits of RJ based on stem cells.
Spontaneous Complete Regression of Colon Cancer Liver Metastases in a Lung Transplant Patient: A Case Report
Authors: Zwart Koen , Ruigrok Dieuwertje , de Graaf-Bos Magda , Goldschmeding Roel , Koopman Miriam , Bol Guus M.
Published: January 2023

Background. Cancer has become an important cause of death in solid organ transplant patients. The cause of malignancies in patients with solid organ transplants is multifactorial, but the use of intensive immunosuppression is regarded as an important factor. We describe the spontaneous, complete regression of colon cancer liver metastases, without initiation of antitumor therapy, in a solid organ transplant patient after modulation of immunosuppressants. Case Presentation. A 59-year-old female was admitted with fever, general discomfort, and elevated liver enzymes. She had received a single lung transplant, five years prior, for end-stage chronic obstructive pulmonary disease. Abdominal ultrasound and a computed tomography scan showed extensive liver lesions, and liver biopsy determined that the lesions were liver metastases originating from a colonic adenocarcinoma. Histopathologic analysis revealed that the primary tumor and liver metastases were mismatch repair-deficient (BRAFV600E mutant and MLH1/PMS2-deficient), also known as a microsatellite instable tumor. The patient’s clinical condition deteriorated rapidly, and she was discharged home with palliative care. No antitumor treatment was initiated. Additionally, there was a short period without any immunosuppressants. Unexpectedly, her clinical condition improved, and complete regression of liver metastases was observed on imaging two months later. Unfortunately, the patient developed rejection of her lung transplant and succumbed to pulmonary disease six months following her cancer diagnosis. The autopsy confirmed the primary colon tumor location and complete regression of >40 liver metastases. Conclusions. Disinhibition and reset of the host immune response could have led to immune destruction of the liver metastases of this patient’s immunogenic dMMR colon carcinoma. This case underscores the huge impact that temporary relief from immunosuppressive therapy could have on tumor homeostasis. Balanced management of care for organ transplant recipients with malignancies requires a multidisciplinary approach involving medical oncologists and transplant physicians to reach the best quality of care in these complex cases.
Targeting RNA Exonuclease XRN1 Potentiates Efficacy of Cancer Immunotherapy
Authors: Ran Xue-Bin , Ding Ling-Wen , Sun Qiao-Yang , Yang Henry , Said Jonathan W. , Zhentang Lao , Madan Vikas , Dakle Pushkar , Xiao Jin-Fen , Loh Xinyi , Li Ying , Xu Liang , Xiang Xiao-Qiang , Wang Ling-Zhi , Goh Boon Cher , Lin De-Chen , Chng Wee Joo , Tan Soo-Yong , Jha Sudhakar , Koeffler H. Phillip
Published: January 2023

Despite the remarkable clinical responses achieved with immune checkpoint blockade therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. Aberrant RNA accumulation can mediate IFN signaling and stimulate an immune response, suggesting that targeting RNA decay machinery might sensitize tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1, as a potential therapeutic target to suppress RNA decay and stimulate antitumor immunity. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy efficacy, while silencing of XRN1 alone did not affect tumor growth in immunodeficient mice. Mechanistically, XRN1 depletion activated IFN signaling and the viral defense pathway; both pathways play determinant roles in regulating immune evasion. Aberrant RNA-sensing signaling proteins (RIG-I/MAVS) mediated the expression of IFN genes, as depletion of each of them blunted the elevation of antiviral/IFN signaling in XRN1-silenced cells. Analysis of pan-cancer CRISPR-screening data indicated that IFN signaling triggered by XRN1 silencing is a common phenomenon, suggesting that the effect of XRN1 silencing may be extended to multiple types of cancers. Overall, XRN1 depletion triggers aberrant RNA-mediated IFN signaling, highlighting the importance of the aberrant RNA-sensing pathway in regulating immune responses. These findings provide the molecular rationale for developing XRN1 inhibitors and exploring their potential clinical application in combination with cancer immunotherapy.

Significance:

Targeting XRN1 activates an intracellular innate immune response mediated by RNA-sensing signaling and potentiates cancer immunotherapy efficacy, suggesting inhibition of RNA decay machinery as a novel strategy for cancer treatment.
A Second Family with Myhre Syndrome Caused by the Same Recurrent SMAD4 Pathogenic Variation (p.Arg496Cys)
Authors: Demir Şenol , Alavanda Ceren , Yeşil Gözde , Aslanger Ayça Dilruba , Ateş Esra Arslan
Published: January 2023

Introduction: Myhre syndrome (MS; OMIM #139210) is a rare connective tissue disorder presenting with cardiovascular, respiratory, gastrointestinal, and skeletal system findings. Fewer than 100 patients were reported until recently, and all molecularly confirmed cases had de novo heterozygous gain-of-function mutations in the SMAD4 gene. Dysregulation of the TGF-beta signaling pathway leads to axial and appendicular skeleton, connective tissue, cardiovascular system, and central nervous system abnormalities. Case Presentation: Two siblings, 12 and 9 years old, were referred to us because of intellectual disability, neurodevelopmental delay, and dysmorphic facial features. Physical examination revealed hypertelorism, strabismus, small mouth, prognathism, short neck, stiff skin, and brachydactyly. Discussion: With a clinical diagnosis of MS, the SMAD4 gene was analyzed via Sanger sequencing, and a heterozygous c.1486C>T (p.Arg496Cys) pathogenic variation was detected in both of the siblings. The segregation analysis revealed that the mutation was inherited from the father who displayed a milder phenotype. Among the 90 patients in the literature, one family was reported in which two siblings carried the same variation (p.Arg496Cys), inherited from the severely affected mother. We are reporting the second family which has three affected family members, a father and two children. We report this study to remind the clinicians to be aware of the parental transmission of SMAD4 variations and also evaluate the parents of the Myhre cases.
The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant
Authors: Buyukdogan Murat , Hancer Veysel Sabri , Sucak Ayhan
Published: January 2023

Introduction: Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. Case Presentation: In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. Whole-exome sequencing was performed; the COG5 gene has shown a pathogenic variant. Discussion: Homozygous patients have never been seen before in the literature for COG5-CDG. We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant.
Two Patients Diagnosed as Succinate Dehydrogenase Deficiency: Case Report
Authors: Ürey Burcu Civelek , Ceylan Ahmet Cevdet , Çavdarlı Büşranur , Çıtak Kurt Ayşegül Neşe , Köylü Oya Kıreker , Yürek Burak , Kasapkara Çiğdem Seher
Published: January 2023

Introductıon: Succinate dehydrogenase deficiency, also known as mitochondrial complex II deficiency, is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial disease. Mutations in the four genes SDHA, B, C,and D have been reported resulting in diverse clinical presentations. The vast majority of clinically affected individuals reported in the literature harbor genetic variants within the SDHA gene and present with a Leigh syndrome phenotype, clinically defined as a subacute necrotizing encephalopathy. Case Report: Herein, we report the first case of a 7-year-old child who was diagnosed as having succinate dehydrogenase deficiency. The affected child presented at 1 year of age with encephalopathy and developmental regression following viral illnesses. MRI changes supported a clinical diagnosis of Leigh syndrome and c.1328C>Q and c.872A>C SDHA variants were identified as compound heterozygous. Mitochondrial cocktail treatment including L-carnitine, riboflavin, thiamine, biotin, and ubiquinone was started. Mild clinical improvement was observed after treatment. He is now unable to walk and speak. The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. Investigations revealed increased lactate level of 67.4 mg/dL (4.5–19.8) with repeatedly increased plasma alanine levels 1,272 µmol/L (200–579). We administered carnitine, coenzyme, riboflavin, and thiamine for empirical therapy with the suspicion of mitochondrial disease. Clinical exome sequencing revealed compound heterozygous variants NM_004168.4:c.1945_1946del (p.Leu649GlufsTer4) at exon 15 of the SDHA gene and NM_004168.4:c.1909-12_1909-11del at intron 14 of SDHA gene. Discussion and Conclusion: There are several very different presentations including Leigh syndrome, epileptic encephalopathy, and cardiomyopathy. Some cases present following viral illness; this feature is not specific to mitochondrial complex II deficiency and occurs in many other mitochondrial disease presentations. There is no cure for complex II deficiency, though some reported patients showed clinical improvement following riboflavin therapy. Riboflavin is not the only therapeutic intervention that is available to patients with an isolated complex II deficiency and various other compounds have shown promise in the treatment of symptoms, including L-carnitine and ubiquinone. Treatment alternatives such as parabenzoquinone EPI-743 and rapamycin are under study in the treatment of the disease.
Morphea – doch eine Systemerkrankung?
Authors: Sticherling Michael
Published: January 2023

Pediatric morphea is an inflammatory, fibrosing dermatologic disorder. Although morphea may be localized to the skin and subcutaneous tissues, differentiating it from systemic sclerosis, there is increasing evidence that morphea is a manifestation of a systemic inflammatory process, with the potential to involve many organ systems. Given the potential risk for irreversible sequelae, pediatric morphea should be treated early and aggressively. Long-term disease monitoring is essential.
Advances and Clinical Trials Update in the Treatment of Diffuse Intrinsic Pontine Gliomas
Authors: Dalle Ore Cecilia , Coleman Christina , Gupta Nalin , Mueller Sabine
Published: January 2023

Background: Diffuse intrinsic pontine gliomas (DIPGs) are high-grade gliomas (HGGs) that occur primarily in children, and represent a leading cause of death in pediatric patients with brain tumors with a median overall survival of only 8–11 months. Summary: While these lesions were previously thought to behave similarly to adult HGG, emerging data have demonstrated that DIPG is a biologically distinct entity from adult HGG frequently driven by mutations in the histone genes H3.3 and H3.1 not found in adult glioma. While biopsy of DIPG was historically felt to confer unacceptable risk of morbidity and mortality, multiple studies have demonstrated that stereotactic biopsy of DIPG is safe, allowing not only for improved understanding of DIPG but also forming the basis for protocols for personalized medicine in DIPG. However, current options for personalized medicine in DIPG are limited by the lack of efficacious targeted therapies for the mutations commonly found in DIPG. Multiple treatment modalities including targeted therapies, immunotherapy, convection-enhanced delivery, and focused ultrasound are in various stages of investigation. Key Message: Increasing frequency of biopsy for DIPG has identified distinct driving mutations that may serve as therapeutic targets. Novel treatment modalities are under investigation.
Regional Persistent Extreme Precipitation Events over Southwest China under Different Low-Latitude Intraseasonal Oscillations during the Rainy Season
Authors: Nie Yanbo , Sun Jianqi
Published: January 2023

This study investigates the mechanisms of low-latitude intraseasonal oscillations affecting regional persistent extreme precipitation events (RPEPEs) over Southwest China (SWC) during rainy seasons. Most of the RPEPEs over SWC are dominated by 7–20-day variability. The RPEPEs over SWC are preconditioned by two different types of 7–20-day Rossby waves with almost opposite phases over the western North Pacific (WNP). The two types of 7–20-day Rossby waves have direct and indirect effects on type-1 and -2 RPEPEs, respectively. For type 1, a coupled 7–20-day low-level anticyclone and suppressed convection originating from the tropical WNP propagate northwestward and cover the region from the South China Sea (SCS) to the Bay of Bengal before the RPEPEs. The anticyclone triggers ascending motion over SWC and transports more moisture to SWC, favoring the SWC RPEPEs. Before the type-2 RPEPEs, a coupled 7–20-day low-level cyclone and enhanced convection propagates from the tropical WNP to the SCS. The enhanced convection over the SCS leads to the westward extension of the western Pacific subtropical high (WPSH) and the eastward shift of the South Asian high (SAH). The variations in the WPSH and the SAH directly cause SWC RPEPEs by inducing ascending motion and transporting moisture. The mechanisms for type-2 RPEPEs tend to work under the background with a strong WPSH. Using a Lagrangian model, we found that both the 7–20-day oscillations and their background atmospheric circulations result in significant differences in moisture sources for the two types of RPEPEs. These findings benefit a better understanding of SWC extreme precipitation events.
ASEAN, COVID-19 and Myanmar crisis: Dealing with critical juncture
Authors: Wicaksana I Gede Wahyu , Nauvarian Demas , Pramudia Putu Shangrina
Published: January 2023

Explaining how international institutions develop is the significant contribution of historical institutionalism (HI) to the study of contemporary world politics. HI offers two important concepts, critical juncture and path dependence, demonstrating dynamics within the institution, leading towards continuity and change. The case of the Association of Southeast Asian Nations (ASEAN) during the COVID-19 pandemic and the Myanmar democratic crisis tells us about the impact of the crucial moments on the regional organisation and its responses. Yet, ASEAN is resistant to change. What makes it possible is the question that cannot be answered by using the HI approach. Hence, we explain by employing a theoretical framework founded upon the link between diplomatic culture and institutional legitimacy, adopted from the English School (ES) theory of International Relations (IR). This article argues that ASEAN's diplomatic culture ensures member countrie’s compliance with the Association's code of conduct and prevents external power intrusion into Southeast Asian affairs and interests. Therefore, ASEAN's institutional legitimacy can be maintained. The Association deals with the critical juncture without undertaking any fundamental change.
Transcranial sonography with clinical and demographic characteristics to predict cognitive impairment in PD: a longitudinal study
Authors: Chen Zhiguang , Zhang Wei , He Wen , Guang Yang , Yu Tengfei , Du Yue , Li Rui
Published: January 2023

Background

Parkinson’s disease (PD) is a neurodegenerative disease and is clinically characterized by a series of motor symptoms (MS) and nonmotor symptoms (NMS). NMS often appear before MS, while cognitive impairment mostly occurs within a few years after the diagnosis of PD. Therefore, we aimed to predict the risk factors for cognitive impairment (CI) in PD patients based on transcranial sonography, clinical symptoms, and demographic characteristics.

Methods

Based on the occurrence time of CI, a total of 172 PD patients were divided into non-CI (N-CI, n = 48), CI at the first treatment (F-CI, n = 58), and CI at the last treatment (L-CI, n = 66) groups. Clinical data (including MS and NMS) and ultrasonic data of all patients at the first treatment and the last treatment were collected retrospectively. Independent samples t tests were used to compare continuous data, and chi-square tests were used to compare categorical data. The risk factors for CI and Parkinson’s disease dementia were identified by logistic regression analysis, and an ROC curve was established to explore the diagnostic efficacy.

Results

1) The age of onset, first treatment and smoking history of CI patients were significantly different from those of N-CI patients. When age of first treatment ≥61 years was considered the boundary value to diagnose CI, the sensitivity and specificity were 77.40 and 66.70%, respectively. 2) The severity of depression was significantly different between F-CI and N-CI patients at the first treatment, while the cumulative and new or aggravated memory deficit was significantly different between the L-CI and N-CI patients at the last treatment. 3) There was a significant difference in TCS grading between the first and last treatment in L-CI patients. 4) Depression, sexual dysfunction, and olfactory dysfunction in NMS were independent risk factors for CI during the last treatment. 5) The sensitivity and specificity of predicting CI in PD patients were 81.80 and 64.60%, respectively.

Conclusions

PD patients with CI were older, and most of them had a history of smoking. Furthermore, there was good diagnostic efficiency for predicting CI in PD via TCS combined with clinical characteristics (especially NMS).
The antimicrobial efficacy of graphene oxide, double antibiotic paste, and their combination against Enterococcus faecalis in the root canal treatment
Authors: Eskandari Fateme , Abbaszadegan Abbas , Gholami Ahmad , Ghahramani Yasamin
Published: January 2023

Background

Inter-appointment medication of the root canals with appropriate intracanal medicaments has been advocated to improve root canal disinfection. Graphene oxide (GO) has shown promising antimicrobial activity against a wide range of microorganisms, besides the capability of carrying antibiotics. The current study aimed to compare the antibacterial activity of double antibiotic paste (DAP) and GO per se and in combination (GO-DAP) against Enterococcus faecalis (E. faecalis).

Methods

A total of 108 extracted human mandibular premolars were contaminated with three-week-old E. faecalis and subjected to a primary microbial assessment. The samples were categorized into 15 groups concerning the intracanal medicament (DAP, GO, GO-DAP, and control) and contact time (1, 7, and 14 days). Then, the root canals were medicated, incubated, and resubjected to a secondary antimicrobial evaluation. The colony-forming units (CFU) were counted to calculate the antimicrobial efficacy. The data were analyzed via the Kruskal–Wallis test (α = 0.05).

Results

GO-DAP was the only medicament that completely eradicated E. faecalis in 1 day. The percentage reduction of CFU/ml in the GO-DAP and DAP groups was higher than that in the GO group at all allocated contact times. Furthermore, a significant decrease of the CFU/ml was seen in the GO and DAP groups after 7 and 14 days of being medicated (P < 0.05).

Conclusion

Since GO-DAP improved root canal disinfection, this novel material can be introduced as a promising intracanal medicament against E. faecalis even in the short run.
Transformational leadership in development of transformative education in nursing: a qualitative study
Authors: Ghorbani Azam , Mohammadi Nooredin , Rooddehghan Zahra , Bakhshi Fatemeh , Nasrabadi Alireza Nikbakht
Published: January 2023

Background

Regarding the dynamic and increasing needs of communities, changes in the education system are essential to train competent healthcare professionals. The study aimed to explore the experience of educational directors, teachers, and students to gain insight into the implementation of educational transformative programs.

Method

A qualitative approach with the grounded theory method was applied in this study. Twenty-four participants were selected by using a purposive and theoretical sampling method. The data were collected from April 2019 to May 2020 in nursing schools of Tehran, through in-depth semi-structured individual face-to-face interviews and field notes. Collected data were analyzed by Corbin and Strauss’s (2015) approach.

Results

In this study, transformational leadership was extracted as the core concept. The core concept emerged from four sub-concepts including transformative management; educational policy requirements; providing a platform and community-centered education.

Conclusions

Nurse educational directors need to achieve some competencies and capabilities for implementing transformative education in nursing schools. Also, achieving a transformative perspective by educational directors is essential.
Qualitative risk assessment of homogeneity, stability, and residual concentrations of antimicrobials in medicated feed and drinking water in pig rearing
Authors: Georgaki Despoina , Vandael Femke , Cardoso de Carvalho Ferreira Helena , Filippitzi Maria Eleni , De Backer Patrick , Devreese Mathias , Dewulf Jeroen , Croubels Siska
Published: January 2023

Background

Despite the common use of oral group treatment in pig rearing, the magnitude of the factors influencing the homogeneity and stability of antimicrobial drugs in medicated feed and medicated drinking water are largely unknown, as well as the residual concentrations of the drugs after the end of the treatment.

Results

This study presents a qualitative risk assessment to estimate the magnitude of the risks for reduced homogeneity and stability, and increased residual concentrations of antimicrobial drugs in medicated feed and drinking water on the farm. Risk assessment was done using a questionnaire and farm visits (n = 52), combined with a second questionnaire, and concentrations of amoxicillin and doxycycline measured in medicated feed and water samples, each collected on 10 farms.

For medicated feed, the duration of storage in the silo did not show to influence the concentration levels in a consistent trend, while the treatment duration had a low to negligible effect. A moderate to high risk was found caused by human error when preparing the medicated feed on the farm. Purchased medicated feed greatly reduces the risk of human error and drugs remain stable during the duration of treatment, while the risk of residual concentrations after the end of the treatment was estimated to be low to moderate. The feed intake variability was identified as a moderate to high risk factor.

For medicated drinking water, the type of dosing pump, age of pre-solution, and human errors during the preparation of the pre-solution present a moderate to high risk on homogeneity and stability. Precipitation of the active substance in the absence of a stirrer in a drinking water tank was shown to be a low to moderate risk factor for residues after treatment. Waterline length had a weak correlation with the concentrations of the antimicrobials, while a moderate to high influence was detected for the water intake by the pigs.

Conclusions

A considerable variation in drug concentration in both medicated feed and medicated drinking water was detected depending on their preparation. Therefore, it is important to know which factors influence the homogeneity and stability, and the residual concentrations after treatment.
Efficient recombinant production of mouse-derived cryptdin family peptides by a novel facilitation strategy for inclusion body formation
Authors: Song Yuchi , Wang Yi , Yan Shaonan , Nakamura Kiminori , Kikukawa Takashi , Ayabe Tokiyoshi , Aizawa Tomoyasu
Published: January 2023

Background

A number of antimicrobial peptides (AMPs) hold promise as new drugs owing to their potent bactericidal activity and because they are often refractory to the development of drug resistance. Cryptdins (Crps) are a family of antimicrobial peptides found in the small intestine of mice, comprising six isoforms containing three sets of disulfide bonds. Although Crp4 is actively being investigated, there have been few studies to date on the other Crp isoforms. A prerequisite for detailed characterization of the other Crp isoforms is establishment of efficient sample preparation methods.

Results

To avoid degradation during recombinant expression of Crps in E. coli, co-expression of Crps with the aggregation-prone protein human α-lactalbumin (HLA) was used to promote the formation of stable inclusion bodies. Using this method, the production of Crp4 and Crp6 by the BL21 strain was effective, but the expression of other Crp isoforms was not as efficient. The results of a cell-free system study suggested that Crps were degraded, even though a substantial amounts of Crps were synthesized. Therefore, using the Origami™ B strain, we were able to significantly increase the expression efficiency of Crps by promoting the formation of erroneous intermolecular disulfide bonds between HLA and Crps, thereby promoting protein aggregation and inclusion body formation, which prevented degradation. The various Crp isoforms were successfully refolded in vitro and purified using reversed-phase HPLC. In addition, the yield was further improved by deformylation of formyl-Crps. We measured the antibacterial activity of Crps against both Gram-positive and Gram-negative bacteria. Each Crp isoform exhibited a completely different trend in antimicrobial activity, although conformational analysis by circular dichroism did not reveal any significant steric differences.

Conclusion

In this study, we established a novel and efficient method for the production of the cryptdin family of cysteine-containing antimicrobial peptides. Additionally, we found that there were notable differences in the antibacterial activities of the various Crp family members. The expression system established in this study is expected to provide new insights regarding the mechanisms underlying the different antibacterial activities of the Crp family of peptides.