bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing maternal phenylketonuria (PKU) syndrome: important factors to achieve good metabolic control throughout pregnancy
Authors: Rohde Carmen , Thiele Alena Gerlinde , Baerwald Christoph , Ascherl Rudolf Georg , Lier Dinah , Och Ulrike , Heller Christina , Jung Alexandra , Schönherr Kathrin , Joerg-Streller Monika , Luttat Simone , Matzgen Sabine , Winkler Tina , Rosenbaum-Fabian Stefanie , Joos Oxana , Beblo Skadi
Published: November 2021

Background

Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Since maintaining or reintroducing the strict phenylalanine (Phe) limited diet in adults with PKU is challenging, we evaluated the most important dietary and psychosocial factors to gain and sustain good metabolic control in phenylketonuric women throughout pregnancy by a questionnaire survey with 38 questions concerning therapy feasibility. Among them, the key questions covered 5 essential items of PKU care as follows: General information about maternal PKU, PKU training, diet implementation, individual metabolic care, personal support. In addition, all participating PKU mothers were asked to estimate the quality of their personal metabolic control of the concluded pregnancies. 54 PKU mothers with 81 pregnancies were approached at 12 metabolic centers in Germany and Austria were included. According to metabolic control, pregnancies of PKU women were divided in two groups: group “ideal” (not more than 5% of all blood Phe concentrations during pregnancy > 360 µmol/l; n = 23) and group “suboptimal” (all others; n = 51).

Results

The demand for support was equally distributed among groups, concerning both amount and content. Personal support by the direct social environment (partner, family and friends) (“suboptimal” 71% vs “ideal” 78%) as well as individual metabolic care by the specialized metabolic center (both groups around 60%) were rated as most important factors. The groups differed significantly with respect to the estimation of the quality of their metabolic situation (p < 0.001). Group “ideal” presented a 100% realistic self-assessment. In contrast, group “suboptimal” overestimated their metabolic control in 53% of the pregnancies. Offspring of group “suboptimal” showed clinical signs of maternal PKU-syndrome in 27%.

Conclusion

The development of training programs by specialized metabolic centers for females with PKU in child bearing age is crucial, especially since those mothers at risk of giving birth to a child with maternal PKU syndrome are not aware of their suboptimal metabolic control. Such programs should provide specific awareness training for the own metabolic situation and should include partners and families.
NeoSeq: a new method of genomic sequencing for newborn screening
Authors: Wang Huaiyan , Yang Yuqi , Zhou Lingna , Wang Yu , Long Wei , Yu Bin
Published: November 2021

Objective

To explore the clinical application of NeoSeq in newborn screening.

Methods

Based on the results obtained from traditional newborn screening (NBS) with tandem mass spectrometry (TMS), three cohorts were recruited into the present study: 36 true positive cases (TPC), 60 false-positive cases (FPC), and 100 negative cases. The dried blood spots of the infants were analyzed with NeoSeq, which is based on multiplex PCR amplicon sequencing.

Results

Overall, the sensitivity of NeoSeq was 55.6% (20/36) in the detection of TPC. NeoSeq detected disease-related genes in 20 of 36 TPC infants, while it could not identify these genes in eight children. Five cases (3.1%) with disease risk were additionally found in the FPC and NC cohorts. There was a significant difference in the diagnostic time between the two methods—10 days for NeoSeq vs. 43 days for traditional NBS.

Conclusions

NeoSeq is an economic genomic screening test for newborn screening. It can detect most inborn errors of metabolism, reduce the rate of false positive results, shorten the porting cycles, and reduce the screening cost. However, it is still necessary to further optimize the panel design and add more clinically relevant genomic variants to increase its sensitivity.
Impaired wakefulness and rapid eye movement sleep in dopamine-deficient mice
Authors: Kashiwagi Mitsuaki , Kanuka Mika , Tanaka Kaeko , Fujita Masayo , Nakai Ayaka , Tatsuzawa Chika , Kobayashi Kazuto , Ikeda Kazutaka , Hayashi Yu
Published: November 2021

Despite the established roles of the dopaminergic system in promoting arousal, the effects of loss of dopamine on the patterns of sleep and wakefulness remain elusive. Here, we examined the sleep architecture of dopamine-deficient (DD) mice, which were previously developed by global knockout of tyrosine hydroxylase and its specific rescue in noradrenergic and adrenergic neurons. We found that DD mice have reduced time spent in wakefulness. Unexpectedly, DD mice also exhibited a marked reduction in the time spent in rapid eye movement (REM) sleep. The electroencephalogram power spectrum of all vigilance states in DD mice were also affected. These results support the current understanding of the critical roles of the dopaminergic system in maintaining wakefulness and also implicate its previously unknown effects on REM sleep.
Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies
Authors: Xiao Xinyi , Huang Shengkang , Chen Sifei , Wang Yazhuo , Sun Qihang , Xu Xinjie , Li Yuhua
Published: November 2021

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this review, we summarize the mechanisms underlying CRS and ICANS and provide potential treatment and prevention strategies.
Analysis of reasons for loss to follow up in a prospective study in Chandigarh, India and impact from telecom changes
Authors: Mathew Joseph L. , Patel Pooja N. , Wagner Abram L. , Suri Vanita , Bharti Bhavneet , Carlson Bradley F. , Boulton Matthew L.
Published: November 2021

Objective

Mobile phones are used in research studies, to enroll and follow-up participants, collect data, and implement mHealth initiatives. We conducted a longitudinal study in a birth cohort, where infants were required to make four scheduled visits by 12 months of age. Families of those failing to attend scheduled follow-up visits, were contacted telephonically to ascertain the reasons, which were categorized as: not interested to continue participating, migrated, phone disconnected due to telecom change, or other reason.

Results

A total of 413 mother-infant dyads were enrolled. The overall attrition was 56%, with majority occurring at the first follow-up visit. This temporally coincided with a telecom service provider announcing strong incentives to switch providers. Attrition monotonically decreased at subsequent visits. The reasons were: moved away (13%), no longer interested (8%), phone disconnected (7%), and multiple other reasons (28%), the majority of whom had unreachable phones. Those who remained in the study and those lost to follow-up were similar on most demographic variables. Among common reasons for attrition in cohort studies, we experienced a new dimension introduced by telecom changes. These findings underscore the need to consider unexpected reasons for attrition in longitudinal studies, and design more robust methods to follow-up participants.
A case of early gastric cancer with a single giant lymph node metastasis
Authors: Yoshikawa Masato , Tamario Misaki , Obatake Masayoshi , Sato Koichi , Yagi Shigehiko , Otani Hiromi , Kito Katsumi
Published: November 2021

Background

Early gastric cancer (EGC) is often associated with lymphatic metastasis, but it is extremely rare to be found as a single giant lymph node. Cancer often becomes more malignant in metastatic lesions than in primary lesions, and retrodifferentiation to the fetal gastrointestinal tract during the metastatic process has been reported in gastric cancer. We report an extremely rare case of EGC with a 13-cm giant lymph node metastasis in which an adenocarcinoma with enteroblastic differentiation and yolk sac tumor-like components was observed.

Case presentation

The case was a 70-year-old man who visited his local doctor with right hypochondrial pain, which was identified by computed tomography (CT) as a giant mass. Upper endoscopy revealed a 30-mm-sized 0-IIc lesion in the greater curvature of the angular incisure and a 15-mm-sized 0-IIa lesion in the anterior wall of the lower body of the gastric body. Endoscopic biopsy revealed tubular adenocarcinoma in both lesions. The gastric lesion and the giant tumor were clinically regarded as independent lesions (gastrointestinal stromal tumor, [GIST], and EGCs), and distal gastrectomy and D1 + dissection were performed to comprehensively treat all lesions. Pathological examination revealed that the giant tumor was tubular adenocarcinoma with an intestinal phenotype and was considered a lymph node metastasis of EGCs. To exclude the possibility of metastasis of adenocarcinoma other than EGCs, postoperative positron emission tomography-computed tomography (PET-CT) and colonoscopy were performed; however, no primary site other than the stomach was found. Metastatic lymph nodes have an increased degree of atypia compared with the primary tumor, and yolk sac tumor-like carcinoma morphology was observed along with α-fetoprotein (AFP) and Spalt-like 4 (SALL4) expression in this case. It was considered that retrodifferentiation to a fetal phenotype occurred during the metastatic process. Liver metastasis occurred 6 months after surgery, and chemotherapy is currently being introduced.

Conclusions

We experienced a case of EGC with a single giant lymph node metastasis. Retrodifferentiation to the fetal gastrointestinal tract during metastasis was speculated to be involved in the formation of giant lymph node metastasis and liver metastasis in this case.
The effect of gender and language proficiency on the metaphor use in the writing of TEFL students
Authors: Fattahi Nazila , Nushi Musa
Published: November 2021

The ubiquitous nature of metaphor in everyday life and its significance in second language learning has triggered plethoric research on the relationship between metaphor and language learning. To contribute to the still growing literature, the current study explore the effect of learner variables, namely gender and proficiency, on metaphor use in TEFL students’ writing. To achieve that objective, 27 intermediate and 23 upper-intermediate Iranian TEFL students were asked to write on an IELTS Writing Task 2 topic. Fifty essays were analyzed for metaphor use through Metaphor Identification Procedure (Pragglejaz Group in Metaphor Symb 22(1):1–39, 2007) and Vehicle Identification Procedure (Cameron in Metaphor in educational discourse, Continuum, London, 2003). The data analyzed through t-test and multiple regression analysis revealed the advantage of upper-intermediate students over intermediate students concerning metaphor use in their writing. Gender, on the other hand, did not play an influential role in the students’ metaphor use. The findings of this research and the implications they might have for the field of English language teaching will be discussed.
Dexmedetomidine versus magnesium sulphate as an adjuvant to local anesthesia in single-injection percutaneous peribulbar anesthesia for cataract extraction
Authors: M. Aya Abuelyossr , Mohammad N. A. , Maghawry Khaled M. , Elderh Maha Sadek , AbdulAziz Mai Mohsen
Published: November 2021

Background

The aim of the study was to evaluate the impact of addition of dexmedetomidine or magnesium sulphate to the standard local anesthetics mixture as a primary objective and to compare between both as a secondary objective utilizing the single-injection percutaneous technique for peribulbar block. In this prospective randomized double-blinded clinical trial (RCT), sixty patients, both sexes, aged 45 to 75, with an ASA of I to III, were scheduled for cataract extraction operation. They were divided into three equal groups; each received a single injection peribulbar block of a mixture of 0.5% bupivacaine (3 ml) + 2 percent lidocaine (3 ml) + 120 IU hyaluronidase + (control group (C): 0.5 ml of normal saline; group D: 50 μg of dexmedetomidine; group M: 50 mg of magnesium sulphate in 0.5 ml) with a total injected volume of 7 ml each. The duration of sensory, motor block, need for supplementary doses, hemodynamics, and satisfaction of patients and surgeons were assessed.

Results

For the primary outcome, both the dexmedetomidine and magnesium groups revealed statistically significant differences from the control group with shorter onsets of sensory block and lid akinesia (p value< 0.001 for both), shorter onset of globe akinesia for dexmedetomidine (p value<0.001) and for magnesium sulphate (p value=0.022), prolonged duration of lid and globe akinesia and sensory block (p value<0.001), better patient satisfaction (p value=0.044) but insignificant difference regarding surgeons’ satisfaction (p value= 0.117) and a less frequent, but statistically insignificant need for supplementary injection (p value=0.075). The demographic and clinical hemodynamics and oxygen saturation parameters were comparable between the three groups. For the secondary outcome, dexmedetomidine was superior to magnesium sulphate regarding onset of globe and lid akinesia (p value= 0.047 and 0.003, respectively), and durations of globe akinesia and sensory block (p value= 0.02 and 0.016, respectively). No complications related to the drugs or procedure were recorded.

Conclusions

When compared to 50 mg magnesium sulphate, dexmedetomidine at a dose of 50 μg is a superior adjunct to local anesthetic combination in peribulbar block for cataract procedures in terms of start and duration of peribulbar block.
Multistage closure of a congenital extrahepatic portosystemic shunt
Authors: Facas João , Cruz Manuel , Costa João Filipe , Agostinho Alfredo , Donato Paulo
Published: November 2021

Background

Congenital extrahepatic portosystemic shunts (CEPS) are rare shunts connecting the extrahepatic portal system with the inferior vena cava. Shunt dimensions and the risk of portal hypertension determines the closure strategy. Endovascular treatment is indicated for single stage occlusion of longer length shunts, whereas the remaining shunt types are preferentially surgically occluded. Herein we describe the technical details of a novel endovascular treatment for short length CEPS.

Case presentation

A 15-years-old male with a short length CEPS complicated with multinodular liver disease was submitted to a multistage closure, as indicated by the high portal pressure values during shunt balloon occlusion venography. Initially a transjugular intrahepatic portosystemic shunt (TIPS) was created and the CEPS occluded with an atrial septal defect occluder. In a second procedure the TIPS was embolized with a flow reductor stent and an amplatzer vascular plug II. At a 1 year follow up the liver nodules size reduced, the patient remains asymptomatic, and the shunt adequately closed.

Conclusion

This paper outlines the potential use of a TIPS and an atrial septal defect occluder combination in complex CEPS, supporting its usage as an alternative to the standard surgical treatment.

Level of Evidence: Level 4, Case report.
Effect of caffeine on delayed-onset muscle soreness: a meta-analysis of RCT
Authors: Muljadi Janisa Andrea , Kaewphongsri Patsorn , Chaijenkij Kornkit , Kongtharvonskul Jatupon
Published: November 2021

Background

There are multiple strategies that have been suggested to attenuate delayed-onset muscle soreness (DOMS). Caffeine has been shown to assist with blocking pain associated with DOMS. However, currently there is still controversy over the effects of caffeine use.

Main body

We conducted a meta-analysis to compare pain associated with muscle soreness by both the VAS and indirect markers by CK of caffeine and placebo after exercise. The meta-analysis was carried out in accordance with the PRISMA guidelines. Relevant studies from Medline and Scopus published up to May 20, 2021, were included, which resulted in a total of 477 and 132 studies being retrieved from Scopus and Medline, respectively. Seven studies met the inclusion criteria, and in these, there were 68 persons in the caffeine group and 74 persons in the placebo group. A visual analog score of muscle soreness was recorded pre-exercise, immediately post-exercise, and at one to four days post-exercise; the scores at these time points in the caffeine group as compared to those in the placebo group progressed from 0.00 (95% CI − 0.51, 0.50) to − 0.20 (− 1.09, 0.69), − 0.92 (− 2.20, 0.36), − 1.02 (− 1.86, − 0.19), 0.00 (− 0.36, 0.36), and 0.18 (− 0.56, 0.92), respectively. No statistically significant differences were noted for CK between the two groups at 24 h post-exercise.

Short conclusion

Our meta-analysis results indicate that caffeine supplements reduce delayed-onset muscle soreness when compared to a placebo 48 h after exercise. However, at 24 h post-exercise, caffeine can reduce DOMS only in people who worked on resistant exercise. The CK used in this meta-analysis did not show any differences.

Trial registration: PROSPERO CRD42021260248.

Level of evidenceI.
Milk microbiome in dairy cattle and the challenges of low microbial biomass and exogenous contamination
Authors: Pollock Jolinda , Salter Susannah J. , Nixon Rebecca , Hutchings Michael R.
Published: November 2021

Background

The blanket usage of antimicrobials at the end of lactation (or “drying off”) in dairy cattle is under increasing scrutiny due to concerns about antimicrobial resistance. To lower antimicrobial usage in dairy farming, farmers are now encouraged to use “selective dry cow therapy” whereby only cows viewed as at high risk of mastitis are administered antimicrobial agents. It is important to gain a better understanding of how this practice affects the udder-associated microbiota and the potential knock-on effects on antimicrobial-resistant bacterial populations circulating on the farm. However, there are challenges associated with studying low biomass environments such as milk, due to known contamination effects on microbiome datasets. Here, we obtained milk samples from cattle at drying off and at calving to measure potential shifts in bacterial load and microbiota composition, with a critical assessment of contamination effects.

Results

Several samples had no detectable 16S rRNA gene copies and crucially, exogenous contamination was detected in the initial microbiome dataset. The affected samples were removed from the final microbiome analysis, which compromised the experimental design and statistical analysis. There was no significant difference in bacterial load between treatments (P > 0.05), but load was lower at calving than at drying off (P = 0.039). Escherichia coli counts by both sequence and culture data increased significantly in the presence of reduced bacterial load and a decreasing trend of microbiome richness and diversity. The milk samples revealed diverse microbiomes not reflecting a typical infection profile and were largely comprised of gut- and skin-associated taxa, with the former decreasing somewhat after prolonged sealing of the teats.

Conclusions

The drying off period had a key influence on microbiota composition and bacterial load, which appeared to be independent of antimicrobial usage. The interactions between drying off treatment protocol and milk microbiome dynamics are clearly complex, and our evaluations of these interactions were restricted by low biomass samples and contamination effects. Therefore, our analysis will inform the design of future studies to establish whether different selection protocols could be implemented to further minimise antimicrobial usage.
Thoracic surgery in the COVID-19 era: an Italian university hospital experience
Authors: Taje Riccardo , Elia Stefano , Cristino Benedetto , Tacconi Federico , Natali Gianluca , Ambrogi Vincenzo , Pompeo Eugenio
Published: November 2021

Background

Aims of this study were to assess the results of anti-COVID19 measures applied to maintain thoracic surgery activity at an Italian University institution through a 12-month period and to assess the results as compared with an equivalent non-pandemic time span.

Methods

Data and results of 646 patients operated on at the department of Thoracic Surgery of the Tor Vergata University Policlinic in Rome between February 2019 and March 2021 were retrospectively analyzed. Patients were divided in 2 groups: one operated on during the COVID-19 pandemic (pandemic group) and another during the previous non-pandemic 12 months (non-pandemic group). Primary outcome measure was COVID-19 infection-free rate.

Results

Three patients developed mild COVID-19 infection early after surgery resulting in an estimated COVID-19 infection-free rate of 98%. At intergroup comparisons (non-pandemic vs. pandemic group), a greater number of patients was operated before the pandemic (352 vs. 294, p = 0.0013). In addition, a significant greater thoracoscopy/thoracotomy procedures rate was found in the pandemic group (97/151 vs. 82/81, p = 0.02) and the total number of chest drainages (104 vs. 131, p = 0.0001) was higher in the same group. At surgery, tumor size was larger (19.5 ± 13 vs. 28.2 ± 21; p < 0.001) and T3-T4/T1-T2 ratio was higher (16/97 vs. 30/56; p < 0.001) during the pandemic with no difference in mortality and morbidity. In addition, the number of patients lost before treatment was higher in the pandemic group (8 vs. 15; p = 0.01). Finally, in 7 patients admitted for COVID-19 pneumonia, incidental lung (N = 5) or mediastinal (N = 2) tumors were discovered at the chest computed tomography.

Conclusions

Estimated COVID-19 infection free rate was 98% in the COVID-19 pandemic group; there were less surgical procedures, and operated lung tumors had larger size and more advanced stages than in the non-pandemic group. Nonetheless, hospital stay was reduced with comparable mortality and morbidity. Our study results may help implement efficacy of the everyday surgical care.
Random-PE: an efficient integration of random sequences into mammalian genome by prime editing
Authors: Jiao Yaoge , Zhou Lifang , Tao Rui , Wang Yanhong , Hu Yun , Jiang Lurong , Li Li , Yao Shaohua
Published: November 2021

Prime editing (PE) enables efficiently targeted introduction of multiple types of small-sized genetic change without requiring double-strand breaks or donor templates. Here we designed a simple strategy to introduce random DNA sequences into targeted genomic loci by prime editing, which we named random prime editing (Random-PE). In our strategy, the prime editing guide RNA (pegRNA) was engineered to harbor random sequences between the primer binding sequence (PBS) and homologous arm (HA) of the reverse transcriptase templates. With these pegRNAs, we achieved efficient targeted insertion or substitution of random sequences with different lengths, ranging from 5 to 10, in mammalian cells. Importantly, the diversity of inserted sequences is well preserved. By fine-tuning the design of random sequences, we were able to make simultaneously insertions or substitutions of random sequences in multiple sites, allowing in situ evolution of multiple positions in a given protein. Therefore, these results provide a framework for targeted integration of random sequences into genomes, which can be redirected for manifold applications, such as in situ protospacer adjacent motif (PAM) library construction, enhancer screening, and DNA barcoding.
Approach to the Patient With Pseudoacromegaly
Authors: Marques Pedro , Korbonits Márta
Published: November 2021

Pseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1. Acromegaloid physical features or accelerated growth in a patient may prompt referral to endocrinologists. Because pseudoacromegaly conditions are rare and heterogeneous, often with overlapping clinical features, the underlying diagnosis may be challenging to establish. As many of these have a genetic origin, such as pachydermoperiostosis, Sotos syndrome, Weaver syndrome, or Cantú syndrome, collaboration is key with clinical geneticists in the diagnosis of these patients. Although rare, awareness of these uncommon conditions and their characteristic features will help their timely recognition.
Glucocorticoid Receptor Antagonist Alters Corticosterone and Receptor-sensitive mRNAs in the Hypoxic Neonatal Rat
Authors: Gehrand Ashley L , Phillips Jonathan , Welhouse Kyle D , Siddiqui Hana , Schulgit Matthew , Hoffman Jeff , Hunt Hazel , Raff Hershel
Published: November 2021

Hypoxia, a common stressor with preterm birth, increases morbidity and mortality associated with prematurity. Glucocorticoids (GCs) are administered to the preterm infant to improve oxygenation; prolonged use of GCs remains controversial. We evaluated a selective glucocorticoid receptor (GR) antagonist (CORT113176) in our neonatal rat model of human prematurity to assess how fasting and hypoxia-induced increases in neonatal corticosterone affects endogenous hormones and endocrine pancreas function. Neonatal rat pups at postnatal day (PD) 2, PD8, and PD15 were pretreated with CORT113176 and, after 60 minutes of separation and fasting, exposed to hypoxia (8% O2) or control (normoxia) for 30 or 60 minutes while fasting was continued. Plasma corticosterone, ACTH, glucose, and insulin were measured and fasting Homeostatic Model Assessment of Insulin Resistance was calculated. Glucocorticoid and insulin receptor-sensitive gene mRNAs were analyzed in liver, muscle, and adipose to evaluate target tissue biomarkers. CORT113176 pretreatment augmented baseline and hypoxia-induced increases in corticosterone and attenuated hypoxia-induced increases in insulin resistance at PD2. Normoxic and hypoxic stress increased the hepatic GR-sensitive gene mRNAs, Gilz and Per1; this was eliminated by pretreatment with CORT113176. CORT113176 pretreatment decreased baseline insulin receptor-sensitive gene mRNAs Akt2, Irs1, Pik3r1, and Srebp1c at PD2. We show that CORT113176 variably augments the stress-induced increases in corticosterone concentrations (attenuation of negative feedback) and that GR is critical for hepatic responses to stress in the hypoxic neonate. We also propose that measurement of Gilz and Per1 mRNA expression may be useful to evaluate the effectiveness of GR antagonism.
Interferon Signaling in Estrogen Receptor–positive Breast Cancer: A Revitalized Topic
Authors: Fu Xiaoyong , De Angelis Carmine , Schiff Rachel
Published: November 2021

Cancer immunology is the most rapidly expanding field in cancer research, with the importance of immunity in cancer pathogenesis now well accepted including in the endocrine-related cancers. The immune system plays an essential role in the development of ductal and luminal epithelial differentiation in the mammary gland. Originally identified as evolutionarily conserved antipathogen cytokines, interferons (IFNs) have shown important immune-modulatory and antineoplastic properties when administered to patients with various types of cancer, including breast cancer. Recent studies have drawn attention to the role of tumor- and stromal-infiltrating lymphocytes in dictating therapy response and outcome of breast cancer patients, which, however, is highly dependent on the breast cancer subtype. The emerging role of tumor cell–inherent IFN signaling in the subtype-defined tumor microenvironment could influence therapy response with protumor activities in breast cancer. Here we review evidence with new insights into tumor cell–intrinsic and tumor microenvironment–derived IFN signaling, and the crosstalk of IFN signaling with key signaling pathways in estrogen receptor–positive (ER+) breast cancer. We also discuss clinical implications and opportunities exploiting IFN signaling to treat advanced ER+ breast cancer.
Retroperitoneal Paraganglioma With Asymptomatic Follicular Lymphoma: A Case Report
Authors: Kakizawa Keisuke , Yamashita Miho , Nakashima Mitsuko , Kawauchi Yuto , Ikeya Akira , Matsushita Akio , Sasaki Shigekazu , Oki Yutaka
Published: November 2021

Paraganglioma (PGL) is a rare tumor originating from extra-adrenal paraganglionic chromaffin tissues, and most sympathetic PGLs have excessive catecholamine secretion. However, nonfunctional PGLs are sometimes found. Although malignant PGL is defined by metastasis to nonchromaffin tissues, it is difficult to predict malignancies due to the lack of reliable markers of potential malignancies. We report the case of a 69-year-old Japanese woman with an incidental retroperitoneal tumor and multiple enlarged mesenteric lymph nodes simultaneously. The patient had no subjective symptoms and there were no laboratory findings suggesting catecholamine hypersecretion. Both the retroperitoneal tumor and the enlarged mesenteric lymph nodes showed high accumulation of fluorodeoxyglucose (FDG), whereas metaiodobenzylguanidine (MIBG) was accumulated only at the retroperitoneal tumor. Although a retroperitoneal tumor was diagnosed as nonfunctional PGL by examination including MIBG scintigraphy, the cause of enlarged mesenteric lymph nodes could not be diagnosed by imaging and biochemical tests. As a result of retroperitoneal tumor resection and mesenteric lymph nodes sampling, histopathological examination revealed that a retroperitoneal tumor was PGL and enlarged mesenteric lymph nodes were follicular lymphoma. To reveal an underlying genetic factor, we performed whole exome sequencing of genomic DNA, and we identified 2 possible candidate variants in SDHD and DLST, but the pathogenicity of these variants remains uncertain in the present case. This rare case reinforces the importance of histopathological diagnosis of nonchromaffin tissue lesions in patients with PGL for the appropriate treatment strategy.
An Approach to the Evaluation and Management of the Obese Child With Early Puberty
Authors: Tenedero Christine B , Oei Krista , Palmert Mark R
Published: November 2021

With the declining age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and management of precocious puberty. We focus on girls as the literature is more robust, but include boys where literature permits.

Suggestions include: (1) Age cutoffs for evaluation of precocious puberty should not differ substantially from those used for nonobese children. Obese girls with confirmed thelarche should be evaluated for gonadotropin-dependent, central precocious puberty (CPP) to determine if further investigation or treatment is warranted. (2) Basal luteinizing hormone (LH) levels remain a recommended first-line test. However, if stimulation testing is utilized, there is a theoretical possibility that the lower peak LH responses seen in obesity could lead to a false negative result. (3) Advanced bone age (BA) is common among obese girls even without early puberty; hence its diagnostic utility is limited. (4) Obesity does not eliminate the need for magnetic resonance imaging in girls with true CPP. Age and clinical features should determine who warrants neuroimaging. (5) BA can be used to predict adult height in obese girls with CPP to inform counseling around treatment. (6) Use of gonadotropin-releasing hormone analogues (GnRHa) leads to increased adult height in obese girls. (7) Obesity should not limit GnRHa use as these agents do not worsen weight status in obese girls with CPP.
Avian ceca are indispensable for hindgut enteric nervous system development
Authors: Nagy Nandor , Kovacs Tamas , Stavely Rhian , Halasy Viktoria , Soos Adam , Szocs Emoke , Hotta Ryo , Graham Hannah , Goldstein Allan M.
Published: November 2021

The enteric nervous system (ENS), which is derived from enteric neural crest cells (ENCCs), represents the neuronal innervation of the intestine. Compromised ENCC migration can lead to Hirschsprung disease, which is characterized by an aganglionic distal bowel. During the craniocaudal migration of ENCCs along the gut, we find that their proliferation is greatest as the ENCC wavefront passes through the ceca, a pair of pouches at the midgut-hindgut junction in avian intestine. Removal of the ceca leads to hindgut aganglionosis, suggesting that they are required for ENS development. Comparative transcriptome profiling of the cecal buds compared with the interceca region shows that the non-canonical Wnt signaling pathway is preferentially expressed within the ceca. Specifically, WNT11 is highly expressed, as confirmed by RNA in situ hybridization, leading us to hypothesize that cecal expression of WNT11 is important for ENCC colonization of the hindgut. Organ cultures using embryonic day 6 avian intestine show that WNT11 inhibits enteric neuronal differentiation. These results reveal an essential role for the ceca during hindgut ENS formation and highlight an important function for non-canonical Wnt signaling in regulating ENCC differentiation.
Andrew Johnson (1958-2021)
Authors: Lloyd Robert , Alberio Ramiro , Crother Brian I.
Published: November 2021

Andrew Johnson, a pioneer in the development of the amphibian axolotl as a model to study the early stages of metazoan development, died 15th September 2021. Known as ‘AJ’ by his family, and by his friends and colleagues, his older sister Pam referred to him as an unstoppable ‘force of nature’ who at the age of 9 or 10 said to her, ‘I'm going to become a professor’. Here, we reflect on AJ's life and work, paying particular attention to his studies on the establishment of primordial germ cells in vertebrates.
Three critical regions of the erythromycin resistance methyltransferase, ErmE, are required for function supporting a model for the interaction of Erm family enzymes with substrate rRNA
Authors: Sharkey Rory E. , Herbert Johnny B. , McGaha Danielle A. , Nguyen Vy , Schoeffler Allyn J. , Dunkle Jack A.
Published: November 2021

6-Methyladenosine modification of DNA and RNA is widespread throughout the three domains of life and often accomplished by a Rossmann-fold methyltransferase domain which contains conserved sequence elements directing S-adenosylmethionine cofactor binding and placement of the target adenosine residue into the active site. Elaborations to the conserved Rossman-fold and appended domains direct methylation to diverse DNA and RNA sequences and structures. Recently, the first atomic-resolution structure of a ribosomal RNA adenine dimethylase (RRAD) family member bound to rRNA was solved, TFB1M bound to helix 45 of 12S rRNA. Since erythromycin resistance methyltransferases are also members of the RRAD family, and understanding how these enzymes recognize rRNA could be used to combat their role in antibiotic resistance, we constructed a model of ErmE bound to a 23S rRNA fragment based on the TFB1M–rRNA structure. We designed site-directed mutants of ErmE based on this model and assayed the mutants by in vivo phenotypic assays and in vitro assays with purified protein. Our results and additional bioinformatic analyses suggest our structural model captures key ErmE–rRNA interactions and indicate three regions of Erm proteins play a critical role in methylation: the target adenosine binding pocket, the basic ridge, and the α4-cleft.
Formation and development of the network self-learning organization
Authors: Belova Elena N.
Published: November 2021

The solution of an urgent socially significant scientific problem based on the implementation of theoretical and methodological, conceptual substantiation, methodological and technological support for the formation and development of a network self-learning organization as a prospect for the development of educational organizations. The concept and model of the formation and development of a networked self-learning organization have been scientifically substantiated, developed and tested. The prospects of using in practice a new scientific idea of ​​the formation and development of a network self-learning organization of additional professional education based on the development of the readiness and ability of its employees to increase the effectiveness of professional activity in the process of their training, mutual learning, self-training and self-development has been developed and proved. The monograph is addressed to teachers, students of psychological and pedagogical directions, graduate students, doctoral students, managers, specialists of educational organizations and a wide range of readers interested in improving the performance of educational organizations through their transformation into network self-learning organizations.
Komunikacja w przestrzeni miejskiej zmieniająca standardy zachowania w dobie pandemii SARS-CoV-2
Authors: Berdychowska Zofia
Published: November 2021

Urban Communication and Its Influence on Standards of Behaviour in the Sars-Cov-2 Pandemic The SARS-Cov-2 virus pandemic made it necessary to implement new standards of behaviour in public spaces. As instruments of communication, brief messages in a generally accessible public space aimed at limiting infections by changing social behaviour. This way, such messages contributed to modifying public space in its physical, social and communicative aspects. The article attempts to capture the communicative and linguistic practices used for this purpose.
Estetyczne akty mowy jako przedmiot pragmalingwistyki: status, funkcje, formy
Authors: Kiklewicz Aleksander , Przybyszewski Sebastian
Published: November 2021

Aesthetic Acts of Speech as a Subject of Pragmalinguistics: Status, Functions, Forms. Part 1 In the paper, the status and features of aesthetic speech acts are discussed. They are a research phenomenon at the junction of two disciplines: pragmatics and stylistics. The authors treat aesthetic speech acts as these kinds of speech acts that are produced by the sender with an intention to make the receiver have an aesthetic experience, however, they are not limited solely to the field of literature. No performative verbs can be ascribed to them, therefore they may be categorized as indirect stimulating acts. Moreover, the aesthetic function performed by such speech acts is frequently accompanied by other linguistic functions.
O coming oucie i wyrażeniach pokrewnych w polszczyźnie
Authors: Zabawa Marcin
Published: November 2021

On coming out and Related Constructions in Polish

The aim of the present paper is to discuss the English lexical borrowing coming out, together with some related constructions, used in Polish. The construction in question was originally used in Polish in LGBT community to denote the process of disclosing one’s own non-heterosexual orientation; now, however, it has significantly expanded its range of contexts. The construction is thus used in many different contexts, connected with e.g. one’s religion, details about one’s earnings, etc. Interestingly enough, the meaning of other constructions, such as outing, has not been extended. In the article, descriptions of the meanings of the forms in question have been illustrated with numerous examples taken from the National Corpus of Polish (NKJP) and the MoncoPL Corpus.
Język i językoznawstwo według Krystyny Pisarkowej (1932–2010)
Authors: Kowalik Krystyna
Published: November 2021

Language and Linguistics According to Krystyna Pisarkowa (1932–2010)

Krystyna Pisarkowa’s rich output is characterised by a variety of forms and a wide range of topics, as well as an innovative interpretation of linguistic phenomena. The following paper can be described as biographical and substantive. The text contains certain facts from Pisarkowa’s life that are connected with certain spheres of her scientific activity in which she succeeded, references to people who played a significant role in her life, as well as development of her research interests. The publications which are mentioned in the paper have been selected according to Pisarkowa’s attitude to language, its essence, pragmatic-functional-stylistic variety, as well as potential context and purpose which lies beyond its typical usage. Moreover, an attempt has been made at reconstructing Pisarkowa’s views on the range, shape and place of linguistics among humanistic disciplines.
Krystyny Pisarkowej odkrywanie Malinowskiego
Authors: Bartmiński Jerzy , Niebrzegowska-Bartmińska Stanisława
Published: November 2021

Krystyna Pisarkowa’s Discovering of Malinowski The article is concerned with the two-volume publication Językoznawstwo Bronisława Malinowskiego [Bronisław Malinowski’s Linguistics], edited by Krystyna Pisarek. Its first volume contains the editor’s thorough analysis of the linguistic achievements of this Polish-born British anthropologist, while the second volume includes translations of Malinowski’s works and a dictionary of the Kiriwina language. The linguistic importance of Malinowski’s works had been underestimated: his articles “Classificatory Particles in the Language of Kiriwina” (1920) and “The Problem of Meaning in Primitive Languages” (1923) were not included in the thirteen-volume collection of his writings (Dzieła [Works]). Pisarkowa, in turn, does recognize Malinowski’s contribution to linguistics and considers the following to be his unique achievements: (1) the discovery of the phatic function of speech (adopted by Roman Jakobson in his classification of language functions); (2) an explicit formulation of the principle of contextualism and the pragmatic aspect of word meaning; and (3) a precise description of the Kiriwina system of classificatory particles.
O Rachunku sumienia jako zadaniu tłumacza Krystyny Pisarkowej
Authors: Tutak Kinga
Published: November 2021

On Rachunek sumienia jako zadanie tłumacza [Examination of Conscience as a Translator’s Task] by Krystyna Pisarkowa

The author of the article tries to reconstruct the way in which Krystyna Pisarkowa perceived confession and examination of conscience. Pisarkowa discussed those forms of confessing one’s sins in a series of lectures, in an article of 2002, and in a book published two years after her death. The main message of these works is the connection between the examination of conscience and translation according to the approach of Walter Benjamin. In the opinion of Pisarkowa, examination of conscience is a complex act of thought and internal speech that needs to be translated into a natural language. Also, Pisarkowa takes into account the second dimension of updating the examination of conscience, which is related to functioning of a certain genre in religious discourse. She provides some examples of old Polish confessions and she analyses them in terms of textology, which deserves our special attention.
„Ile przemilczam, tego nie wypowiem”: o (prze)milczeniu w utworach Wisławy Szymborskiej i ich przekładzie na język niemiecki
Authors: Kubaszczyk Joanna
Published: November 2021

“How Much I Dissemble I shall not Utter”: on Aposiopesis in the Poems by Wisława Szymborska and Their Translation into German

Krystyna Pisarkowa emphasises the importance of means which participate in shaping the expression of emotions in a poetic text, and calls for extracting from the text “essential ingredients from seemingly minor semantic accents” (Pisarkowa 1998: 36). In this article, the author takes this inspiration and analyses how Wisława Szymborska applies silence in her poems as an aesthetic category and an expression of choked emotions, what indicators of silence she uses, and what happens with this silence in the translation of her poems into German by Karl Dedecius. The author concludes that a translator should be able to empathise with emotions and be an intermediary not only for the word, but also for the unspoken.
Can Facing the Truth Improve Outcomes? Effects of Information in Consumer Finance
Authors: Fong Jessica , Hunter Megan
Published: November 2021

This article explores when consumers avoid learning information about their credit scores and how viewing one’s credit score impacts future credit scores.
Prevalência de hipofosfatemia e risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva
Authors: Bezerra Alexandra Rodrigues , Santos Paloma Arquimedes Alves dos , Santos Leidiane Silva , Petribú Marina De Moraes Vasconcelos
Published: November 2021

Introdução: A presença de hipofosfatemia é fortemente relacionada à ocorrência de síndrome de realimentação em pacientes críticos, na qual um dos principais grupos de risco é a população idosa. Objetivos: Avaliar a prevalência de hipofosfatemia e o risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva. Métodos: Estudo observacional prospectivo, realizado numa unidade de terapia intensiva com pacientes idosos de ambos os sexos e em uso de terapia nutricional enteral. Foram coletados dados demográficos, clínicos e exames bioquímicos, e realizadas triagem e avaliação nutricional. As necessidades nutricionais foram calculadas e adotou-se o ponto de corte de 90% para estabelecer a adequação da oferta calórica. Para avaliar o risco e a ocorrência de síndrome de realimentação, foram utilizados os critérios propostos pelo grupo NICE. A análise estatística foi realizada com o auxílio do programa SPSS 13.0, com um intervalo de confiança (IC) de 95%. Resultados: Foram estudados 44 pacientes, dos quais 34,1% estavam em magreza; 86,4% dos pacientes iniciaram a terapia nutricional enteral em até 48 horas, com 43,2% de adequação calórica em até 72 horas. A hipofosfatemia foi encontrada em 9,1% dos pacientes na admissão e em 29,5% após o início da dieta. Com isso, 88,6% dos pacientes apresentaram algum risco para desenvolver síndrome de realimentação e 40,9% deles manifestaram a síndrome. Conclusão: Foi identificada elevada prevalência de hipofosfatemia após o início da terapia nutricional. Além disso, o risco de desenvolver síndrome de realimentação foi elevado e sua manifestação se assemelha aos dados encontrados na literatura.
Escolhas alimentares no contexto de um município com relevante produção agrícola: a perspectiva dos ambientes alimentares em Palmeira das Missões, RS
Authors: Bueno Marilene Cassel , Ruiz Eliziane Nicolodi Francescato , Cruz Fabiana Thomé da
Published: November 2021

Introdução: Os ambientes alimentares podem ser entendidos como o contexto em que os indivíduos acessam e realizam suas escolhas alimentares, podendo favorecer ou não a alimentação saudável e adequada. Objetivo: Analisar as escolhas alimentares de consumidores urbanos na perspectiva de ambientes alimentares em Palmeira das Missões, no Rio Grande do Sul. Métodos: Estudo de abordagem qualitativa, que utilizou como técnica de pesquisa entrevista semiestruturada com consumidores residentes na área urbana no município. Os dados foram analisados por meio da análise de conteúdo por categorias temáticas, a partir das dimensões física, econômica, política e sociocultural, as quais compõem os ambientes alimentares. Resultados e Discussões: As escolhas alimentares estão interseccionadas com a ampla disponibilidade e facilidade para encontrar mais alimentos ultraprocessados do que in natura, bem como com as condições econômicas, que se tornam limitadoras das escolhas alimentares pautadas na variedade e inclusão de alimentos in natura e minimamente processados. Constatou-se a importância do Programa Bolsa Família para a aquisição de alimentos, sobretudo para famílias de menores estratos socioeconômicos. Considerações finais: Os dados da pesquisa indicam que escolhas alimentares que incluem maior variedade e disponibilidade de alimentos in natura estão associadas principalmente às condições econômicas e à disponibilidade desses alimentos. Por isso, destaca-se a importância do fortalecimento de políticas públicas para a promoção da alimentação adequada e saudável, bem como a relevância da articulação de ações locais, tendo em vista o potencial agrícola do município.