bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel fission yeast platform to model N-glycosylation and the bases of congenital disorders of glycosylation type I
Authors: Gallo Giovanna L. , Valko Ayelen , Herrera Aguilar Nathalia , Weisz Ariel D. , D'Alessio Cecilia 
Published: December 2021

ABSTRACT
Congenital disorders of glycosylation type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe strains that synthesize all possible theoretical combinations of LLOs containing three to zero glucose (Glc) residues and nine to five mannose (Man) residues. The occurrence of unexpected LLOs suggested the requirement of specific Man residues for glucosyltransferase activities. We then quantified protein hypoglycosylation in each strain and found that in S. pombe the presence of Glc in the LLO is more relevant to the transfer efficiency than the number of Man residues. Surprisingly, a decrease in the number of Man residues in glycans somehow improved the glycan transfer. The most severe hypoglycosylation was produced in cells that synthesized LLOs completely lacking Glc and having a high number of Man residues. This deficiency could be reverted by expressing a single-subunit oligosaccharyltransferase with a broad range of substrate specificity. Our work shows the usefulness of this new S. pombe set of mutants as a platform to model the molecular bases of human CDG-I diseases.
This article has an associated First Person interview with the first authors of the paper.
A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics
Authors: Zwyer Michaela , Çavusoglu Cengiz , Ghielmetti Giovanni , Pacciarini Maria Lodovica , Scaltriti Erika , Van Soolingen Dick , Dötsch Anna , Reinhard Miriam , Gagneux Sebastien , Brites Daniela 
Published: December 2021

Background: The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis. Methods: We gathered a total of 8,736 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 829 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups. Results: We propose to divide M. bovis, M. caprae and M. orygis in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These sublineages differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These markers were implemented in KvarQ and TB-Profiler, which are platform-independent, open-source tools. Conclusions: Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies.
Detection of aging in the common explosive RDX using terahertz time-domain spectroscopy
Authors: Yan Zhijin , Shi Wei 
Published: December 2021

A method to detect the aging in cyclotrimethylene-trinitramine (RDX), using terahertz (THz) waves, is reported in this paper. The absorption spectra of RDX are analyzed, and any changes of the characteristic absorption peaks (before and after aged treatment of RDX in laboratory) are compared. When RDX samples undergo aging, the characteristic absorption peaks (at 1.02 THz, 1.36 THz, 1.58 THz, and 2.37 THz) disappear, which corresponds to the fracture of N-

N
O

2

bonds in RDX molecules. These results show that THz time-domain spectroscopy technology may be used not only for analysis but also for detection of aging in RDX and similar materials.
The reliability of the angle of deviation measurement from the Photo-Hirschberg tests and Krimsky tests
Authors: Tengtrisorn S. , Tungsattayathitthan A. , Na Phatthalung S. , Singha P. , Rattanalert N. , Bhurachokviwat S. , Chouyjan S. 
Published: December 2021

Objective
To compare the angle of deviation measured from Photo-Hirschberg testing and Krimsky testing, with that from an alternate prism cover test (APCT) in strabismus patients.

Methods
A cross-sectional study was conducted in Songklanagarind Hospital, Thailand. Thirty-three strabismus patients were photographed for analysis by Photo-Hirschberg testing using computer software. The corneal light reflex displacement, converted into prism diopter (PD), was compared to the angle of deviation measured with APCT. Twenty-eight strabismus patients were tested with the Krimsky test. Data were analyzed using Pearson correlation and paired t-tests. The study excluded 4 intermittent exotropia cases, 1 intermittent esotropia case and 2 which cases missing data for krimsky test.

Results
The mean±SD of the deviation angle, measured by APCT with a fixation target at 30 cm and 6 m; were 48.09±16.34PD and 47.82±15.73 PD, respectively. At 1 m, the difference in the angle of deviation measured from APCT and the Photo-Hirschberg test within 10 PD were 58.8% and 63.6%, for ET and XT, respectively. The difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 86.7% and 80.0%, respectively. At 4 m, the difference in angle of deviation measured from APCT and Photo-Hirschberg tests within 10 PD in ET and XT were 58.8% and 54.5%, respectively; whereas, the difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 80.0% and 70.0%, respectively.

Conclusion
The reliability of Krimsky test was better than Photo-Hirschberg test for measuring an angle of deviation.
Factors associated with early receipt of COVID-19 vaccination and adherence to second dose in the Veterans Affairs healthcare system
Authors: Ioannou George N. , Green Pamela , Locke Emily R. , Berry Kristin 
Published: December 2021

Background
We aimed to determine factors independently associated with early COVID-19 vaccination and adherence to two-dose regimens.

Methods
Among persons receiving care in the Veterans Affairs (VA) healthcare system (n = 5,766,638), we identified those who received at least one dose of COVID-19 vaccination through the VA, during the first ~3months following emergency use authorization, from December 11, 2020 to March 9, 2021 (n = 1,569,099, or 27.2%, including 880,200 (56.1%) Moderna, 676,279 (43.1%) Pfizer-BioNTech and 12,620 (0.8%) Janssen vaccines).

Results
Follow-up for receipt of vaccination began on December 11, 2020. After adjustment for baseline characteristics ascertained as of December 11, 2020, factors significantly associated with vaccination included older age, higher comorbidity burden, higher body mass index category, Black (vs. White) race (adjusted hazard ratio [AHR] 1.19, 95% CI 1.19–1.20), Hispanic (vs. non-Hispanic) ethnicity (AHR 1.12, 95% CI 1.11–1.13), urban (vs. rural) residence (AHR 1.31, 95% CI 1.31–1.31), and geographical region, while AI/AN race (vs. White), was associated with lower vaccination rate (AHR 0.85, 95% CI 0.84–0.87). Among persons who received both doses of Moderna or Pfizer-BioNTech vaccines, 95.3% received the second dose within ±4 days of the recommended date. Among persons who received the first vaccine dose, only 3.2% did not receive the second dose within 42 days for Pfizer versus 4.0% for Moderna (p<0.001). Factors independently associated with higher likelihood of missing the second dose included younger age (10.83% in 18–50 yo vs. 2.72% in 70–75 yo), AI/AN race, female sex, rural location, geographical region and prior positive test for SARS-CoV-2.

Conclusions
We identified sociodemographic and clinical factors that may be used to target vaccination efforts and to further improve adherence to second vaccine dosing.
P002 Psychiatric Comorbidity and Suicide in Childhood Onset Immune-Mediated Diseases —A Systematic Review and Meta-Analysis
Authors: Jansson Sabine , Malham Mikkel , Wewer Vibeke , Rask Charlotte 
Published: December 2021

BACKGROUND:
The course of paediatric onset immune mediated inflammatory diseases (IMID) is both physically and mentally challenging. Emotional distress with anxiety and depressive symptoms is commonly reported, however, data on diagnosed comorbid psychiatric disorders is scarce. The aim of this study was to provide a literature overview of psychiatric comorbidity, suicide rates, and their potential risk factors, in childhood onset IMID.

METHODS:
This was a systematic review following the PRISMA guidelines. The protocol was registered at Prospero (ID: CRD42021233890). A literature search was made in the databases Pubmed, PsychINFO, and Embase. We included the following IMID: paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases. Studies that provided prevalence rates of diagnosed psychiatric disorders and/or suicide, were included. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) reported by three or more studies, within the same IMID, were calculated using random-effects meta-analysis. Two authors independently evaluated risk of bias using the New-Castle Ottawa scale.

RESULTS:
Twenty-three studies met the inclusion criteria; 13 describing psychiatric disorders in pIBD and 10 in RD. No study reported on psychiatric disorders in autoimmune liver diseases. Compared to controls without somatic disease, IMID patients had an increased risk of psychiatric disorders, with anxiety and mood disorders being the most common. Prevalence rates for anxiety and mood disorders in pIBD were 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI:12%-26%), respectively, in studies using psychiatric assessment. In RD pooled estimates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders. Based on single studies, risk of suicide was increased in pIBD, but not in juvenile idiopathic arthritis, the most common RD.

CONCLUSION:
In this systematic review, patients with childhood onset IMID had increased prevalence of psychiatric disorders compared to controls. However, only pooled estimates on emotional disorders were possible and studies investigating broad spectrum of psychiatric disorders are needed.
P005 Influence of Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases on the Level of Immunoglobulins G After a Coronavirus Infection
Authors: Knyazev Oleg , Kagramanova Anna , Lishchinskaya Albina , Chernova Marina , Demchenko Alexandra , Babayan Anait , Parfenov Asfold 
Published: December 2021

BACKGROUND:
Currently, there are differences in the results of international studies and treatment outcomes in patients with inflammatory bowel disease (IBD) and COVID-19. Further research is needed to help answer the questions: Do IBD patients have an increased risk of contracting SARS-CoV-2? Do IBD patients have more severe COVID-19 outcomes? Does IBD therapy increase the risk of infection? Do any IBD treatments protect against COVID-19?

OBJECTIVE:
To study the effect of immunosuppressors, genetically engineered biologics, and janus kinase blockers on the level of SARS-CoV-2 class G immunoglobulins in IBD patients who underwent COVID-19.

METHODS:
The level of SARS-CoV-2 class G immunoglobulins was analyzed in 66 patients with IBD after COVID-19 infection, 28 males (42.4%) and 38 women (57.6 %). The median age was 39±4.2 years. The duration of the anamnesis ranged from 1 to 8 years (Iu 4 years). The patients were divided into two groups, depending on the therapy performed: Group 1 (n = 31) received long-term (more than 1 year) immunosuppressants (azathioprine/6-mercaptopurine/tofacitinib), group 2 (n = 35) received anti-TNF-α therapy. The level of SARS-CoV-2 class G immunoglobulins was determined by the immunochemiluminescence method.

RESULTS:
After 4-6 weeks, a twice negative smear of PCR was taken from the nose and oropharynx for SARS-CoV-2 in patients (n=31) receiving anti-relapse therapy with systemic IBD (azathioprine/6-mercaptopurine) and selective (tofacitinib) immunosuppressants, and the average level of Ig G was 44.1 ± 9.8 U/l. Among patients with IBD receiving anti-TNF-α drugs (n = 35), the average level of class G immunoglobulins was 133.6 ± 14.4 U/l. The difference was statistically significant (p = 0.000003).

CONCLUSION:
The level of class G immunoglobulins 3-4 weeks after the COVID-19 infection was significantly higher in IBD patients who received anti-TNF-α drugs.
P010 Precision Dosing Tool Forecasts Trough Infliximab and Associates With Disease Status in Inflammatory Bowel Diseases
Authors: Dervieux Thierry , Primas Christian , Panetta John , Mould Diane , Eser Alexander , Reinisch Walter 
Published: December 2021

BACKGROUND:
Substantial inter- and intra-individual variability of infliximab (IFX) pharmacokinetics (PK) necessitates tailored dosing approaches. Here, we evaluated the performances of a Model Informed Precision Dosing (MIPD) Tool in forecasting trough Infliximab (IFX) levels in association with disease status and circulating TNF-α in patients with Inflammatory Bowel Diseases (IBD).

METHODS:
Consented patients undergoing every 8-week maintenance therapy with IFX were enrolled. Midcycle specimens were collected, IFX, antibodies to IFX, albumin were determined and analyzed with weight using nonlinear mixed effect models coupled with Bayesian data assimilation to forecast trough levels. Accuracy of forecasted as compared to observed trough IFX levels were evaluated using Demings regression. Association between IFX levels, CRP-based clinical remission and TNF-α levels were analyzed using logistic regression and linear mixed effect models.

RESULTS:
In 41 patients receiving IFX (median dose = 5.3 mg/Kg), median IFX levels decreased from 13.0 to 3.9 µg/ml from mid to end of cycle time points, respectively. Midcycle IFX levels forecasted trough with Deming’s slope = 0.90 and R2 =0.87. Observed end cycle and forecasted trough levels above 5µg/mL associated with CRP-based clinical remission (OR = 7.2 CI95%: 1.7-30.2; OR = 21.0 CI95%: 3.4-127.9, respectively) (p < 0.01). Median TNF-α levels increased from 4.6 to 8.0 pg/ml from mid to end of cycle time points, respectively (p < 0.01). CRP and TNF-α levels associated independently and additively to decreased IFX levels (p < 0.01).

CONCLUSION:
These data establish the value of our MIPD tool in forecasting trough IFX levels in patients with IBD. Serum TNF-α and CRP are reflective of inflammatory burden which impacts exposure.
P012 Efficacy of Exclusive Enteral Nutrition and Weekly Adalimumab Combination in Crohn's Patients With Fibroinflammatory Stenosis
Authors: Tokmak Salih 
Published: December 2021

BACKGROUND:
Clinical remission can be achieved with exclusive enteral nutrition (EEN) in patients with Crohn's Disease with different sites of involvement, varying severity, and complications such as abscess and fistula. In the CHARM study, weekly or every other week administration of adalimumab (ADA) did not provide a significant difference in remission rates. Nevertheless, the subgroup analysis showed that in patients with anti-TNF experience, moderate-to-severely active disease, and high CRP values, rates of remission were significantly higher with weekly doses. Our aim was to determine the efficacy of EEN and weekly adalimumab combination in Crohn's patients with fibroinflammatory stenosis.

METHODS:
Seven consecutive patients with newly diagnosed severe disease and fibro-inflammatory stenosis were included in this retrospective study. The PRO-2 score was used to assess clinical remission, the SES-CD score to determine the severity of endoscopic activity, the Nancy score to determine the severity of inflammation in tissue samples, and the MaRIA score to determine changes in magnetic resonance enterography (MRE). Nestle Modulen® (35kcal/kg) was used for twelve weeks as the EEN solution. In addition to the formulation, patients were only allowed to consume water. At the end of the 12th week, the patients gradually switched to a standard diet. Concomitantly initiated ADA was continued at 40 mg weekly after standard loading doses of 160 mg-80 mg-40 mg. The patients were evaluated with clinical and laboratory findings at the 1st, 4th and 8th weeks of the treatment, and also with colonoscopy and MRE at the 12th week.

RESULTS:
The difference between mean PRO-2 score (24.7 ± 1.97, 20.1 ± 1.63, 15.3 ± 1.81,11.4 ± 2.15, 5 ± 1.1, p = 0.031), CRP (14.3 ± 4.54, 11.2 ± 3.31, 6.92 ± 2.88, 2.16 ± 1.14, 0.25 ± 0.13, p = 0.022), albumin (2.9 ± 0.21, 3.05 ± 0.33, 3.4 ± 0.29, 4.1 ± 0.45, 4.6 ± 0.27, p = 0.044), hemoglobin (11.38 ± 0.97, 12.65 ± 0.87, 13.41 ± 0.91, 13.89 ± 0.76, 14.44 ± 0.65, p = 0.063), SES-CD score (17.14 ± 4.87, 7.66 ± 5.98, p = 0.014), MaRIA score (21.13 ± 7.42, 9.91 ± 4.55, p = 0.003) and Nancy score (3.71±0.48, 1.71±0.36, p=0.028) were all statistically significant. The stenotic segment endoscopically passed at week 12 in every patient but one, which had minimally invasive surgery (ileoascendostomy) because of ileus that developed at the eighth week of therapy. Of note, the patient who underwent surgery had perianal involvement.

CONCLUSION:
Despite the extremely limited number of patients and short-term follow-up results, 12-week EEN and concurrent weekly ADA therapy may be effective in inducing remission in this group of patients. There is a need for large-scale, prospective studies on this subject.
P017 Increased Level of Immunoglobulin G in the Development of Adverse Reactions in Patients With Ulcerative Colitis
Authors: Zvyaglova Mariya , Knyazev Oleg , Noscova Karina 
Published: December 2021

BACKGROUND:
Goal: To identify the relationship between the level of immunoglobulins G and E and the development of adverse reaction (AR) in patients with ulcerative colitis (UC) receiving original infliximab (IFХ) and infliximab biosimilar (BS).

METHODS:
35 UC patients with moderate to severe course of the disease (according to Truelove–Witts) who received maintenance therapy with IFХ at a standard dose of 5 mg/kg of body weight for a year were retrospectively analyzed. There were 16 men (45.7%), 19 women (54.3%). The average age is 34±4.2 years. The duration of the anamnesis was from 3 to 7 years. Patients were divided into 3 groups depending on the development of AR and the received biological drug, without taking into account concomitant anti-inflammatory therapy. The 1st group (n=14) alternated the introduction of the original IFХ and its BS; The 2nd group (n=7) consisted of patients alternating between the original IFХ and BS, in whom AR was registered; the 3rd group (n=14) received BS by one trade name. Using enzyme immunoassay, the level of immunoglobulins in the groups of patients was assessed.

RESULTS:
In the 1st and 3rd groups, AR was not observed. AR in 2nd group was characterized by: bronchospasm 3 (42.8%), Quincke's edema 1 (14.3%), urticaria 1 (14.3%), rhinitis 1 (14.3%), anaphylactic shock 1 (14.3%). In patients of 1st group, the level of IgE is 44.8 ± 5.1 IU/ml, IgG is 16.5 ± 1.7 g/l. In 2nd group -IgE-44.5 ± 11.7 IU / ml, IgG-26.1 ± 2.1 g/l, while in patients in group 3-IgE - 31.5 ± 3.04 IU/ml, IgG – 9.46 ± 1.01 g/l. It was reliably established that the highest level of IgG was observed in the 2nd group, while in the 3rd group it was minimal (p < 0.05). The IgG level in 1st group is higher than in 3rd group, although in both groups the IgG level was within the reference values. In all groups, the IgE value remained normal.

CONCLUSION:
AR on the background of therapy with IFL and biosimilars are not associated with an increase in the level of IgE, but are caused by an increase in the level of IgG. The alternation of the original drug and the biosimilar increases the risk of developing AR due to increased IgG levels. Treatment with a biosimilar by one trade name does not increase the risk of developing AR.
P019 Not All Fecal Calprotectin is Specific for Inflammatory Bowel Disease
Authors: Gueorguieva Iana , Jacobs Randall , Piper Marc 
Published: December 2021

CASE:
Introduction:Fecal calprotectin is a known inflammatory marker used to evaluate patients with Inflammatory Bowel Disease (IBD). In fact, ACG Clinical Guideline for management of Crohn’s disease recommend fecal calprotectin (FC) as a helpful test to distinguish IBD versus functional disorder such as Irritable Bowel Syndrome. Studies have also shown association of fecal calprotectin with colon cancer. Recent study proposed fecal calprotectin could be a reliable marker for ruling out organic disease with high negative predictive value.

CASE DESCRIPTION:
We present a patient case of a Caucasian, thirty-five years of age male with PMHx of GERD on Prilosec who presented due to acute abdominal pain, nausea, emesis and watery, nonbloody diarrhea of four days duration. Initially, patient had unknown family history of colon cancer which later was revealed that patient’s father had a colon cancer diagnosis in his fifties. On admission, patient had stable vitals with routine labs showing leukocytosis, iron deficiency anemia, normal CRP, and elevated fecal calprotectin of 986mcg/gm. Abdominal imaging with CT abdomen with contrast showed diffuse dilation of ileum and thickening of the distal ileum up to the level of the ileocecal junction, suggestive of enteritis from infectious or inflammatory etiology such as Crohn’s. Patient was managed conservatively, stool studies were negative otherwise and discharged with outpatient endoscopy due to high suspicion for Inflammatory Bowel Disease. Within one week, patient had a subsequent readmission for now partial small bowel obstruction at the level of ileum. Due to high suspicion of Crohn’s, patient was empirically started on IV steroids. Decision for inpatient colonoscopy was made with colonoscopy showing completely obstructing, circumferential, large mass found in the cecum extending into ascending colon. Final pathology revealed invasive mucinous adenocarcinoma, moderately differentiated. Patient subsequently underwent right hemicolectomy with lymph node resection and adjuvant chemotherapy treatment for stage 3 colon.

DISCUSSION:
We present here a case where a common cancer was found in an otherwise healthy, young male with acute abdominal pain and altered bowel habits. While initial symptoms, imaging and laboratory findings pointed towards a biased high suspicion for Inflammatory Bowel Disease, patient's ultimate diagnosis was stage 3 adenocarcinoma of colon requiring surgical resection and chemotherapy. Fecal calprotectin is a known marker for colon inflammation and associated with both IBD and colon cancer. It is important to keep in mind that while fecal calprotectin may have elevated negative predictive value and be used to rule out organic disease, elevation of fecal calprotectin is not always specific for IBD. We want to emphasize the importance of considering colon cancer on the differential despite a patient’s age and diagnostic bias. Lastly, we also want to highlight the importance of tissue diagnosis prior to long term therapy use.