bluuebunny/crossref_metadata_2025 huggingface dataset:
Hotspot of de novo telomere addition stabilizes linear amplicons in yeast grown in sulfate-limiting conditions
Authors: Hoerr Remington E , Eng Alex , Payen Celia , Di Rienzi Sara C , Raghuraman M K , Dunham Maitreya J , Brewer Bonita J , Friedman Katherine L
Published: January 2023

Evolution is driven by the accumulation of competing mutations that influence survival. A broad form of genetic variation is the amplification or deletion of DNA (≥50 bp) referred to as copy number variation (CNV). In humans, CNV may be inconsequential, contribute to minor phenotypic differences, or cause conditions such as birth defects, neurodevelopmental disorders, and cancers. To identify mechanisms that drive CNV, we monitored the experimental evolution of Saccharomyces cerevisiae populations grown under sulfate-limiting conditions. Cells with increased copy number of the gene SUL1, which encodes a primary sulfate transporter, exhibit a fitness advantage. Previously, we reported interstitial inverted triplications of SUL1 as the dominant rearrangement in a haploid population. Here, in a diploid population, we find instead that small linear fragments containing SUL1 form and are sustained over several generations. Many of the linear fragments are stabilized by de novo telomere addition within a telomere-like sequence near SUL1 (within the SNF5 gene). Using an assay that monitors telomerase action following an induced chromosome break, we show that this region acts as a hotspot of de novo telomere addition and that required sequences map to a region of <250 base pairs. Consistent with previous work showing that association of the telomere-binding protein Cdc13 with internal sequences stimulates telomerase recruitment, mutation of a four-nucleotide motif predicted to associate with Cdc13 abolishes de novo telomere addition. Our study suggests that internal telomere-like sequences that stimulate de novo telomere addition can contribute to adaptation by promoting genomic plasticity.
Age-Related Differences in Responses to Social Exclusion: Active Regulation Matters
Authors: Liao Shuyao , Tang Wei , Zhang Xin
Published: January 2023

Objectives

Although previous studies have reached a consensus that older adults have weaker responses to social exclusion than younger adults, the underlying mechanism is still under debate. The present study examined the age-related differences in responses toward social exclusion with self-report scales and electrodermal activity measurements, aiming at a further understanding of the possible mechanism behind these behaviors.

Methods

Sixty-nine younger (aged 16–28, Mage = 20.13) and 71 older adults (aged 55–82, Mage = 66.72) completed a Cyberball task to simulate social exclusion. They were then asked to regulate the exclusion experiences with different strategies (affect-focused attention/detached reappraisal/distraction strategies) in a subsequent regulation session. Their electrodermal activities were measured throughout the entire process. Self-report scales were measured after the Cyberball session and at the end of the regulation session.

Results

Similar to previous studies, older adults exhibited a lower level of responsiveness toward social exclusion in both self-report scales and electrodermal activities. Moreover, during the Cyberball session, older adults exhibited a tendency of increased electrodermal activity, followed by a decrease in activity. Younger adults demonstrated a pattern of continuous increase. In the regulation session, younger adults from the detached reappraisal regulation strategy condition mimicked the overall response pattern of older adults, such that they exhibited lower levels of responsiveness toward social exclusion.

Discussion

The results from the present study indicate that active emotion regulation (i.e., detached reappraisal) in appraisal stage rather than declined cognition might account for the age-related differences in responses toward social exclusion between older and younger adults.
A molecular phenotypic map of malignant pleural mesothelioma
Authors: Di Genova Alex , Mangiante Lise , Sexton-Oates Alexandra , Voegele Catherine , Fernandez-Cuesta Lynnette , Alcala Nicolas , Foll Matthieu
Published: January 2023

Background

Malignant pleural mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole-genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients.

Results

We first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multiomic MPM datasets (n = 374 in total), we provide an extensive molecular phenotype map of MPM based on the multitask theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (https://tumormap.ucsc.edu/?p=RCG_MESOMICS/MPM_Archetypes ).

Conclusions

This new high-quality MPM multiomics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies.
DEVELOPMENT OF A NOVEL DRUG DELIVERY SYSTEM (DDS) TO DELIVER DRUGS DIRECTLY TO THE COLONIC MUCOSA TO IMPROVE EFFICACY AND REDUCE SYSTEMIC EXPOSURE FOR THE TREATMENT OF ULCERATIVE COLITIS (UC)
Authors: Lee Shaoying Nikki , Stork Cheryl , Razag Ghesal , Quintana Nelson , Wahl Chris , Singh Sharat
Published: January 2023

The clinical remission rate in moderate to severe ulcerative colitis (UC) and Crohn’s Disease (CD) has plateaued at ~15-20% despite the approval of multiple therapeutics. Research has shown that an inadequate amount of drug at the disease site in the colon may be responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to autonomously identify colon entry based on gastrointestinal (GI) anatomy, independent of the variable GI physiological conditions deliver a bolus dose of a liquid drug formulation to the colon mucosa to improve efficacy and reduce systemic toxicity. Here, we aim to evaluate the safety, tolerability, and functionality of a single dose of the DDS using gamma scintigraphy images as a reference in both normal healthy volunteers (NHV) (PM-601) and subjects with active UC (PM-602) in a fasted state.

A total of twelve NHV (N=12) and seven subjects with an endoscopically confirmed history of UC and active UC (N=7) status, defined as having a Mayo score ≥ 2 or elevated fecal calprotectin protein or high sensitivity C-reactive protein within one month of the screening visit, were enrolled and dosed in these studies. Each subject fasted overnight and was dosed with a single DDS device before resuming a normal diet at 4 hours post-dose. Each device was filled with radioactive marker indium-111 DTPA and co-administered with water to which technetium-99m DTPA was added to monitor device GI transit and payload release in the GI tract. The GI transit of the device and delivery location of the radioactive payload were confirmed by serial scintigraphy imaging and compared with the localization data recovered from the devices.

GI transit metrics showed a more variable GI motility and frequent bowel movements were observed among active UC subjects compared to NHV (Table 1). The DDS device was well tolerated in both NHV and active UC subjects. One subject with active UC (PM-602) experienced mild intermittent abdominal cramping following device administration possibly related to the device, which resolved on the same day. No other device-related AEs were reported in these studies. The results from these two studies demonstrated a total of 17 out of 19 DDS devices (90%) successfully identified colon entry and 15 out of 19 DDS devices (79%) delivered the radio payload into the colon regardless of variable GI transit time, the level of inflammation, or the presence of blood in the stool (Table 1 & 2). The dispersion of the radiotracer adequately covered the colon from the site of release throughout the remainder of the colon.

These results demonstrated that the DDS device was well-tolerated and functioned as intended to deliver radiotracer throughout the colon regardless of variable GI motility, disease, and inflammation status.
DRUG INTERACTION BETWEEN PAXLOVID AND TACROLIMUS IN AN ADOLESCENT WITH INFLAMMATORY BOWEL DISEASE
Authors: Zaarur Leenoy , Patel Ashish , Pasternak Brad
Published: January 2023

The coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 virus led to a worldwide pandemic. Emergency use of an investigational medication, Paxlovid, was approved for patient 12 and older who tested positive for COVID-19 and at high risk for severe infection. Inflammatory Bowel Disease (IBD) is a chronic condition causing inflammation in the gastrointestinal tract. Ulcerative Colitis (UC) is a type of IBD centralized in colon and commonly treated with Immunosuppressive drugs.

We present an adolescent with UC treated with paxlovid due to being on tacrolimus who developed with suspected tacrolimus toxicity.

CASE REPORT: A 13-year-old female with UC presented to the ED with vomiting and fatigue after paxlovid ttreatment for COVID. The patient’s UC treatment included tacrolimus along with ustekinumab. She had been diagnosed with SARS-CoV-2 and prescribed Paxlovid bid x 5 days due to immunosuppressive status. Tacrolimus was held during treatment. Once paxlovid completed, tacrolimus was restarted. Two days later, patient presented to ER for vomiting, fatigue, headaches and myalgia. Labs revealed a tacrolimus level of >60 ng/ml . Electrolytes and Creatinine were normal. Toxicology felt this was due to interaction between paxlovid and tacrolimus. Patient advised to hold tacrolimus for 48 hours and repeat levels were 15.8 ng/mL. Symptoms resolved and level repeated three days later and was 2.9 ng/mL

DISCUSSION: Tacrolimus is an immunosuppressant, commonly used for management of organ transplants but also been found effective in treatment of IBD. Tacrolimus requires close monitoring as toxicity may lead to acute or chronic kidney disease. The normal concentration is between 5-15 ng/mL.

Due to rapid escalation of the COVID-19 pandemic, Paxlovid was approved for emergency use for treatment of high-risk patients. It is administered as a 5-day oral course consisting of nirmatrelvir and ritonavir. Our patient was prescribed Paxlovid due to risk secondary to immunosuppression. She was appropriately instructed to stop tacrolimus. Ritonavir is a cytochrome P450 3A inhibitor and can increase plasma concentration of tacrolimus. She restarted tacrolimus treatment 12 hours after her last dose of Paxlovid and presented with symptoms and a level consistent with toxicity. This level was concluded to be due to drug interaction between tacrolimus and Paxlovid. After further withholding of tacrolimus, symptoms improved, and levels normalized. Previous reports in transplant population stress importance of decreasing the dose of tacrolimus or withholding during the course of paxlovid treatment. This case demonstrates the importance of not only ceasing tacrolimus when administering paxlovid, but continuing discontinuation for longer period post completion of therapy to minimize interactions.
THE UTILITY OF BIOPSYING ENDOSCOPICALLY NORMAL APPEARING TERMINAL ILEUM
Authors: Vora Haily , Ibrahim Ramez , Johanna Chan , Farraye Francis , Al Hashash Jana
Published: January 2023

INTRODUCTION

The terminal ileum is often evaluated during colonoscopy procedures. A common indication for endoscopic examination and biopsy of an endoscopically normal appearing terminal ileum is in patients with inflammatory bowel disease (IBD). 1 In patients without IBD, indications for biopsying an endoscopically normal appearing terminal ileum are less clear and may be associated with increased cost and healthcare utilization, as well as increased levels of anxiety for patients. In this study, we aim to determine the indications for examining and biopsying an endoscopically normal appearing terminal ileum in patients without IBD and if, upon review of these biopsies, there is change in management.

METHODS

This was a retrospective chart review of patients who underwent colonoscopy with terminal ileum biopsy at Mayo Clinic between 1/1/2021 and 6/30/21. Patients were excluded if they had a history of IBD, prior ileocecal resection, or an endoscopically abnormal terminal ileum. Clinical and laboratory data, as well as outcomes of interest, were obtained from the electronic medical record. Comparisons between patients were performed using Pearson’s chi-square, Student’s and Mann-Whitney tests.

RESULTS

A total of two hundred consecutive patients were identified as having had biopsies from their endoscopically normal appearing terminal ileum. After reviewing the charts, 69 met inclusion criteria. Of the 69 patients, the majority were female (68.1%) and white (89.9%). Nearly half the patients had a BMI of 30 or above (49.3%). The most common indication for colonoscopy among these patients was chronic diarrhea followed by abdominal pain and hematochezia. Terminal ileum mucosa was histologically abnormal in 6 patients (8.7%): four patients had chronic ileitis, one had acute ileitis, and one had acute and chronic ileitis. All patients with either chronic or acute ileitis had chronic diarrhea listed as an indication for their colonoscopy. The patient with acute and chronic ileitis underwent colonoscopy for suspected Crohn’s disease due to incidental asymptomatic findings of small bowel inflammation on CT enterography.

CONCLUSIONS

In patients with a normal appearing terminal ileum, clinically significant histologic abnormalities on biopsies were found in a small percentage of patients. Although our sample size is small, there may not be diagnostic and therapeutic utility to routinely biopsy endoscopically normal appearing terminal ileum in patients, even in those with chronic diarrhea. Large prospective studies are needed to further support this observation.

REFERENCES

1McHugh, Jonathan B et al. “The diagnostic value of endoscopic terminal ileum biopsies.” The American journal of gastroenterology vol. 102,5 (2007): 1084-9.
A DIET AND LIFESTYLE-FACTOR INTERVENTION PROGRAM TO IMPROVE NUTRITIONAL STATUS, SYMPTOMS, AND QUALITY OF LIFE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Rogers Joseph , Rogers Brittany
Published: January 2023

BACKGROUND

This study sought to evaluate the impact of an evidence-based diet and lifestyle-factor intervention program on nutrition status, symptoms and quality of life of patients with IBD.

METHODS

In this retrospective observational study, de-identified medical records from patients with a self-reported diagnosis of IBD were analyzed. All patients included in the study completed an intervention program consisting of 12 to 24 one-on-one counseling sessions with an IBD-focused registered dietitian in a group-practice setting. Measures collected at baseline and at the conclusion of the program were SIBDQ, MUST, patient-reported symptoms, bowel movement frequency and consistency, measures of stress, fatigue, sleep quality as well as risk of eating and feeding disorders (NIAS-9, EAT-26).

RESULTS

67 patients met the inclusion criteria for the study. Patients with MUST scores >0 at baseline had significantly decreased MUST scores at the end of the program (p=0.004). IBD-related quality of life scores were significantly higher (mean improvement of 18.6 points) at the end of the program compared to baseline (p<0.001). 67 out of 67 patients (100%) reported fewer symptoms at the end of the program with the most improvements related to cramping (97.1%), nausea (94.4%), and fatigue (93.8%). 96.4% of patients experiencing >3 bowel movements per day (BMPD) at baseline decreased their BMPD by the end of the program with 75% experiencing ≤ 3 BMPD. Patients also significantly improved their sleep quality (p<0.001), fatigue level (p<0.001), and stress levels (p<0.001).

CONCLUSIONS

This study demonstrates the potential of a nutrition and lifestyle-factor intervention program to improve IBD patient outcomes. Further study is needed to validate these outcomes alongside a comparable control population and in other patient populations such as those associated with a health plan or employer.
AN UNUSUAL MANIFESTATION OF METASTATIC CROHN’S DISEASE: A CASE REPORT
Authors: Ashrafinia Narges , Guzowski Tomasz
Published: January 2023

INTRODUCTION

Crohn’s Disease (CD) is a chronic granulomatous inflammatory disease involving any section of the gastrointestinal (GI) tract. Metastatic Crohn’s Disease (MCD) is a rare extraintestinal manifestation of CD defined as cutaneous granulomatous lesions non-adjacent to the GI tract. We present a case of suppurative lymphadenitis as a presentation of MCD. This has not yet been reported in the literature.

CASE REPORT

A 22-year-old female with a history of iron deficiency anemia and left calf abscess, secondary to Methicillin-Resistant Staphylococcus Aureus (MRSA) infection, was diagnosed with ileocolonic CD at 18. Her CD was complicated by strictures and abdominal and left tubo-ovarian abscesses with a fistula to the sigmoid. She underwent Ileocolonic resection, sigmoid colectomy and left salpingo-oophorectomy. Histology of the ovarian abscesses unveiled granulation tissue with pseudocysts. Azathioprine and Infliximab were started. At 20, the patient reported acute onset of swelling and pain on the left side of her neck. She denied any constitutional symptoms, sick person or animal contacts, travel, use of recreational drugs and sexual activities. Physical exam was remarkable for a tender, rubbery, 2-centimetre left cervical lymph node. The neck Ultrasound showed cervical lymphadenitis. Antibiotic was started and later extended to target resistant infections. Despite this, she reported worsening symptoms. Computed Tomography of the neck noted a collection suggestive of suppurative lymphadenitis. Incision and Drainage (I & D) of the abscess was done; MRSA was detected. Histology exposed necrotizing granulomata encircled by palisading histocytes and giant cells. There was no evidence of dysplasia, fungal, acid-fast bacilli or spirochetes. Further, Human Immunodeficiency Virus serology, Interferon-Gamma Release Assay and chest radiograph were unremarkable. Later, she underwent surgical excision revealing a fistula to the lower mandible. A drain was placed and then removed upon recovery. Meantime, her CD stayed stable; Infliximab was held till the completion of antibiotics. A year later, she reported a tender, swollen lump on the left side of her groin with an ultrasound confirming inguinal suppurative lymphadenitis. Antibiotics were started, and I &D was done for lasting symptoms. The culture and histology were similar to the previous. Considering the history of CD and histology findings, MCD was concluded as the etiology of this patient’s recurrent MRSA abscesses.

CONCLUSION

Patients on biologic therapy are immunocompromised and presumed high risk for super-infections. In a setting of a persistent infection, despite antibiotics, the possibility of MCD as the cause of lymphadenitis should be raised to cue the clinician to alter therapy and address the MCD within a multidisciplinary setting.
SOCIALLY VULNERABLE PATIENTS WITH INFLAMMATORY BOWEL DISEASE ARE AT INCREASED RISK FOR VACCINE PREVENTABLE ILLNESS
Authors: Jordan Ariel , Sheehan Jessica , Newman Kira , Eloubeidi Dala , Johnson Laura , Higgins Peter
Published: January 2023

INTRODUCTION

Inflammatory bowel disease (IBD) affects patients across diverse ethnic, minority, cultural, and socioeconomic backgrounds; however, the relationship between these social determinants of health (SDOH) and IBD outcomes is not well-studied. SDOH have a known impact on disparities in vaccination, but these effects may be more salient in the IBD population where patients are at greater risk for vaccine-preventable illness from immunosuppressive therapies. The social vulnerability index (SVI) is a tool provided by Centers for Disease Control that can identify individuals at risk for health care disparities by estimating neighborhood-level social need on a 0-1 scale (higher scores indicating greater social vulnerability). Utilizing census tract-level SVI data, we aimed to identify the relationship between the SDOH and vaccination rates in patients with IBD.

METHODS

We used a retrospective cohort design of patients seen at a single IBD center between 01/01/2015 and 08/31/2022. Using the current address listed in the electronic medical record, we geocoded patients to individual census tracts and linked them to corresponding SVI and subscales (Figure 1). Controlling a priori for age, gender, race, ethnicity, marital status, English proficiency, electoral district, and religious affiliation, we used multivariable linear regression to examine the relationship between SVI and vaccination against influenza, Covid-19, pneumococcal pneumonia (conjugate and polysaccharide), and Zoster.

RESULTS

15,245 patients with IBD were included and the percent of unvaccinated individuals was high across all vaccine types: flu (42.8%), Covid-19 (50.9%), pneumonia (62.4%), and Zoster (89.6%). High total levels of social vulnerability were associated with lower vaccination rates across all vaccine groups: flu (B -1.3, 95% CI -1.5, -1.2, p<0.001), Covid-19 (B -0.99, 95% CI -1.1, -0.88), p<0.001), pneumonia (B -0.21, 95% CI -0.27, -0.14, p<0.001), Zoster (B -0.23, 95% CI -0.27, -0.19, p<0.001). On SVI sub-scales, high scores in Socioeconomic Status, Household Composition, and Housing/Transportation were important predictors of vaccine uptake while Minority Status/Language was non-significant (Table 1).

CONCLUSION

Living in a socially vulnerable community is associated with lower vaccination rates across all vaccine types. Higher scores on neighborhood level Socioeconomic Status, Household Composition, and Housing/Transportation were also associated with lower vaccine uptake. Many factors may affect why socially vulnerable patients are under-vaccinated, including a lack of patient and provider knowledge of routine vaccines, lack of access to care, and poor trust in vaccines and healthcare system. Further research is needed improve IBD health maintenance in gastroenterology clinics and ensure equitable distribution of vaccines to socially vulnerable patients.
SEX-BASED DIFFERENCES IN DRUG DURABILITY AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASES
Authors: Tirath Ankita , Arora Jyoti , Ciorba Matthew , Deepak Parakkal
Published: January 2023

BACKGROUND

With an increasing number of therapeutic options to treat IBD, identification of patient-specific factors predictive of drug efficacy is crucial. Sex has been postulated to play a role in response to therapy with possible proposed mechanisms including sex-based hormones and microbiome and epigenetic differences. However, prior clinical data on drug durability stratified by sex are mixed and limited.

METHODS

Using the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry, we analyzed time to drug discontinuation for female versus male patients started on a new IBD medication (including biologic and small molecule therapy) after enrollment between 2016 and August 2022. Drug persistence was examined using Kaplan-Meier plots. A Cox regression model was used to adjust for baseline differences in Crohn’s disease phenotype, rates of perianal disease, and concurrent immunomodulator use. A marginal means/rates model was used to adjust for within-patient correlation given that 252 patients had multiple medication starts.

RESULTS

A total of 1185 patients were identified with 1492 unique new medication starts (n=830 female, 662 male). In this sample, male patients had more complex Crohn’s disease phenotype and higher rates of perianal disease and concurrent immunomodulator use. No significant difference was seen in 12 month drug therapy survival rates based on sex (67.5% females, 65.7% males). Median drug continuation time was 33.5 months in females (95% CI 25.8, 37.4) and 24.5 months in males (95% CI 20.3, 32.8). No difference was seen in anti-TNF and small molecule subgroup analyses. Cox model adjusted for baseline differences in disease severity showed no significant different in probability of drug discontinuation per unit time in females compared to males [HR (95% CI) = 0.95 (0.75-1.21)].

CONCLUSION

Both males and females have similar rates of IBD drug durability over time. The reasons for drug discontinuation should be explored in further studies as this may aid physicians in clinical decision-making.
The Prevalence of Inflammatory Bowel Disease in Greenland
Authors: Gantzel Rasmus Hvidbjerg , Vesterdal Jos Dalvad , Haase Anne-Mette , Petersen Alice Juhl , Grønbæk Henning , Pedersen Michael Lynge
Published: January 2023

Background

Inflammatory bowel disease (IBD) is sparsely investigated in Arctic populations. The aim of this study was to estimate the prevalence of ulcerative colitis (UC) and Crohn’s disease (CD) in Greenland.

Methods

Cross-sectional nationwide data on demography, anthropometry, biochemistry, and pharmacotherapy were extracted from the electronic medical records in Greenland. Diagnoses of UC and CD were based on International Classification of Diseases–Tenth Revision and International Classification of Primary Care–Second Edition coding and treatment with mesalazine. Data from Statistics Greenland were used for prevalence calculations.

Results

In total, 254 patients in Greenland experienced IBD, with 214 cases of UC and 40 cases of CD. The overall IBD prevalence was 0.45%, distributed as 0.38% with UC and 0.07% with CD. The IBD prevalence was similar across the 5 regions of Greenland. However, a higher prevalence was observed in the region main towns with the largest populations (0.53%) compared with the small towns along the coastline (0.29%). UC patients were prescribed mesalazine treatment with a frequency of 78%. Furthermore, 10% of all IBD patients received treatment with nonspecific immunomodulators and 7% received biologics.

Conclusions

This study estimates the prevalence and uncovers characteristics of IBD in Greenland. Although CD may be underdiagnosed or less prevalent, the overall prevalence of IBD in Greenland parallels Scandinavian countries and North America. These results boost the knowledge on autoimmune diseases in arctic populations and may guide clinicians in their management of IBD in Greenland. Furthermore, the results may encourage research in IBD across the Arctic regions.
Industrial policy, local firm growth paths, and capability building in low-income countries: lessons from Ethiopia’s floriculture export sector
Authors: Melese Ayelech T , Whitfield Lindsay
Published: January 2023

The industrial policy literature has made important contributions to understanding how to catalyze industrialization, but it tends to focus more on the industrial policies required to incentivize learning than on studying firm-level learning dynamics and investments in technological capabilities. Furthermore, global value chain studies on export sectors in low-income countries rarely consider whether local firms are part of broader business groups and if so, how that position within business groups affects local firms’ business strategies regarding the global supply chain in question as well as investments outside it. This article examines local firms’ investments in a new export industry, and they are shaped by dynamics linked to their family business groups, industrial policies, and the wider national economic and political contexts of low-income countries. It does so through a case study of Ethiopia and the emergence of its floriculture export industry. The article explains firm-level motivations in acquiring knowledge and building capabilities as well as their export trajectories and firm growth paths and how they are shaped by owners’ decisions related to the overall business group. It argues that industrial policies need to consider not only the existing capabilities, organizations, and networks of local firms but also tailor industrial policies to the potential of the family business groups to drive capability building in new industries.
Intra-atrial coronary artery reconstruction during surgery for cardiac angiosarcoma
Authors: Liu XinPei , Liang YingXiang , Miao Qi
Published: January 2023

A cardiac angiosarcoma is usually located in the right atrium and tends to involve the right coronary artery. Our goal was to report a novel reconstruction technique after en bloc resection of a cardiac angiosarcoma with right coronary artery invasion. This technique includes orthotopic reconstruction of the invaded artery and atrial patch suturing onto the epicardium lateral to the reconstructed right coronary artery. Intra-atrial reconstruction with an end-to-end anastomosis can enhance the graft patency compared to a distal side-to-end anastomosis and can reduce the risk of anastomotic stenosis. Moreover, suturing the graft patch to the epicardium did not increase the risk of bleeding because the pressure in the right atrium was low.
Evaluation of Strontium Interference in Calcium Measurement Procedures and Content in Supplements as Measured by ICP-MS
Authors: Williams Grace R , Downs John W , Wolf Carl E , Cumpston Kirk L , Tobarran Natasha , Wills Brandon K , Bachmann Lorin M
Published: January 2023

Background

Bone health supplements containing strontium are available without prescription, however, the effects of strontium interference on clinical laboratory calcium measurement procedures are unknown.

Methods

To evaluate strontium interference on total calcium measurements, plasma pools with exogenously added strontium were measured by 3 total calcium measurement procedures. For ionized calcium measurements, whole blood pools prepared with exogenously added strontium were measured by 2 ionized calcium measurement procedures. An inductively coupled plasma mass spectrometry assay (ICP-MS) was validated for research measurements of strontium content in commercially available supplements.

Results

Exogenous strontium addition to plasma caused positive bias for total calcium measurements. Strontium concentrations of 1.0 mg/dL (0.114 mmol/L), 2.5 mg/dL (0.284 mmol/L), and 5.0 mg/Dl (0.568 mmol/L) resulted in mean biases of 1.9% to 3.5%, 4.9% to 9.0%, and 10.8% to 19.2%, respectively, for total calcium measurement procedures. Biases for ionized calcium measurements were less than 4.5% for a strontium concentration of 5.0 mg/dL (0.568 mmol/L). An in-house–developed ICP-MS assay for strontium in commercially available supplements exhibited within-laboratory and within-run coefficients of variation of less than 3%, and a linear response was obtained over the assay analytical measurement range of 10 to 100 000 ng/mL (0.0001 to 1.141 mmol/L). Strontium recovery for the ICP-MS assay was 97.1% to 105.3%. The largest amount of strontium measured in dietary supplements was 395 mg in a 1054 mg tablet.

Conclusions

Some dietary supplements contain larger amounts of strontium than indicated on the product label. High concentrations of strontium may cause significant interference for total calcium measurement procedures, but ionized calcium measurement procedures are not significantly affected.
Effect of a biosynthetic bacterial 6-phytase on the digestibility of phosphorus and phytate in midlactating dairy cows
Authors: Dersjant-Li Yueming , Kok Ivonne , Westreicher-Kristen Edwin , García-González Rubén , Mereu Alessandro , Christensen Trine , Marchal Leon
Published: January 2023

The effect of a biosynthetic bacterial 6-phytase (PhyG) on the digestibility and excretion of crude protein (CP), phosphorus (P), and phytate-P (PP) in midlactating dairy cows was investigated. Thirty Holstein-Friesians were assigned to three treatments with 10 cows per treatment in a randomized block design. Cows were fed forage (grass and corn silage) provided ad libitum, and a concentrate (without added inorganic phosphate) administered separately in amounts individualized per cow according to milk production, supplemented with phytase according to treatment. The formulated forage-to-concentrate-ratio was ~65%:35%. Dietary treatments comprised the control diet (CON) and CON supplemented with 2,000 (PhyG2,000) or 5,000 (PhyG5,000) phytase units (FTU)/kg DM in the total diet. The experiment comprised an 18-d preperiod for the collection of data to facilitate the allocation of cows to the treatments, followed by a 19-d experimental period comprising a 14-d diet adaptation period and 5 d of twice daily feces collection. Fecal samples were analyzed for the determination of apparent total tract digestibility (ATTD) of chemical constituents in the diet. The ATTD of PP was 92.6% in CON suggesting a high but incomplete degradation of phytate by ruminal microbial phytases. Cows fed PhyG2,000 exhibited increased ATTD of CP and PP [68.4% (2.7% points above CON) and 95.1% (2.5% points above CON), respectively] whilst PhyG5,000 further increased ATTD PP and also increased ATTD P [54.1% (7.8% points above CON)]; ATTD of Ca tended to be increased in PhyG5,000 vs. CON. Linear dose–response relationships were observed for ATTD of DM, CP, P, Ca, and PP. In addition, fecal excretion of P, and PP linearly reduced and that of Ca and CP tended to linearly reduce with increasing PhyG dose level. No difference was observed for DM intake and milk composition was unaffected except for milk protein which tended to be higher in cows fed PhyG5,000 than CON. In summary, the addition of exogenous phytase at 2,000 FTU/kg or higher to diets of lactating dairy cows improved P, PP, Ca, and CP digestibility and reduced fecal excretion of P, PP, and CP in a dose-dependent manner.
Forward Guidance and Household Expectations
Authors: Coibion Olivier , Georgarakos Dimitris , Gorodnichenko Yuriy , Weber Michael
Published: January 2023

We compare causal effects of forward guidance about future interest rates on households’ expectations of inflation and nominal mortgage rates to the effects of communication about inflation in a randomized control trial using more than 20,000 U.S. consumers in the Nielsen Homescan Panel. We elicit consumers’ expectations, and then provide 22 different forms of information regarding past, current, and/or future interest rates and inflation. Information treatments about current or future interest rates all have similar and offsetting effects on interest rate and inflation expectations, yielding limited pass-through into perceived real rates. Information about mortgage rates has much more powerful effects on interest rate perceptions, with no offsetting effects on inflation expectations, thereby delivering much larger changes in perceived real rates. Revisions in perceived real rates causally lead to changes in the ex-post purchases of durable goods by households.
The Interplay between International Humanitarian Law and International Environmental Law
Authors: van Steenberghe Raphaël
Published: January 2023

It is well known that armed conflicts may cause extensive damage to the environment and that International Humanitarian Law (IHL) is lacking any adequate protection against such damage. International Environmental Law (IEL) could therefore be used to fill the gaps. This nonetheless raises the complex issue of the interplay between that body of law and IHL. This article intends to provide a comprehensive framework on such interplay, the originality of which is to draw inspiration from the relationship between IHL and International Human Rights Law (IHRL). It examines two processes through which IEL may impact the regulation of armed conflict: the ‘interpretation process’, whereby IHL is interpreted in light of IEL, and the ‘application process’, whereby IEL applies alongside IHL to activities related to armed conflicts. While both processes involve the operation of formal mechanisms, including the lex specialis principle and the principle of systemic integration, they must be guided by substantial considerations, which seek coherence between the two bodies of law.
Who finds the short proof?
Authors: Benzmüller Christoph , Fuenmayor David , Steen Alexander , Sutcliffe Geoff
Published: January 2023

This paper reports on an exploration of Boolos’ Curious Inference, using higher-order automated theorem provers (ATPs). Surprisingly, only suitable shorthand notations had to be provided by hand for ATPs to find a short proof. The higher-order lemmas required for constructing a short proof are automatically discovered by the ATPs. Given the observations and suggestions in this paper, full proof automation of Boolos’ and related examples now seems to be within reach of higher-order ATPs.
In memoriam: Filippo Rossi (1926–2022)
Authors: Pick Edgar
Published: January 2023

Description of the scientific life of Filippo Rossi, who died in October 2022.
Diet flexibility of wolves and black bears in the range of migratory caribou
Authors: Bonin Michaël , Dussault Christian , Taillon Joëlle , Pisapio John , Lecomte Nicolas , Côté Steeve D
Published: January 2023

The diet of predators can be highly variable, which is exemplified by their ability to acclimate to a wide range of ecological conditions. Such flexibility in foraging may be a key aspect of their performance in unpredictable environments such as at the edge of the range of a species or where food availability varies greatly in time and space. Gaining information on the diets of predators under such conditions could foster our comprehension of their ecological flexibility and the potential role of predation on the population dynamics of prey. We determined the diet of wolves (Canis lupus) and black bears (Ursus americanus) in northern Québec and Labrador (Canada) within the range of two migratory caribou (Rangifer tarandus) herds: the high-abundance Rivière-aux-Feuilles herd (RFH) and low-abundance Rivière-George herd (RGH). Worldwide, decline in caribou populations has become a concern, stressing the need to better understand the factors involved in these declines, including predation. In northern Québec (RFH range), caribou was the primary year-round prey of wolves while moose (Alces alces) and muskoxen (Ovibos moschatus) were consumed in some sectors. The diet of wolves in northern Labrador (RGH range) varied seasonally, with caribou, moose, and fish as main prey during different periods throughout the year. Black bear diets varied seasonally and regionally. Among the foods we analyzed, caribou was the main source of animal protein for bears in northern Québec and northern Labrador, except during a high abundance of Ungava collared lemming (Dicrostonyx hudsonius). Only bears in northern Québec ate caribou during late summer/fall. Our results highlight the diet flexibility of wolves and black bears in northern food webs, and how their diets change in relation to the distribution and abundance of prey. Our results will help quantify the potential impact of these predators on prey populations in northern systems.
Extension-based semantics for incomplete argumentation frameworks: properties, complexity and algorithms
Authors: Mailly Jean-Guy
Published: January 2023

Incomplete Argumentation Frameworks (IAFs) have been defined to incorporate some qualitative uncertainty in abstract argumentation: information such as ‘I am not sure whether this argument exists’ or ‘I am not sure whether this argument attacks that one’ can be expressed. Reasoning with IAFs is classically based on a set of completions, i.e. standard argumentation frameworks (AFs) that represent the possible worlds encoded in the IAF. The number of these completions may be exponential with respect to the number of arguments in the IAF. This leads, in some cases, to an increase of the complexity of reasoning, compared to the complexity of standard AFs. In this paper, we follow an approach that was initiated for Partial Argumentation Frameworks (PAFs) (a subclass of IAFs), which consists in defining new forms of conflict-freeness and defense, the properties that underly the definition of Dung’s semantics for AFs. We generalize these semantics from PAFs to IAFs. We show that, among three possible types of admissibility, only two of them satisfy some desirable properties. We use them to define two new families of extension-based semantics. We study the properties of these semantics, and in particular, we show that their complexity remains the same as in the case of Dung’s AFs. Finally, we propose a logical encoding of these semantics, and we show experimentally that this encoding can be used efficiently to reason with IAFs, thanks to the power of modern SAT solvers.
Social Justice, Privilege, and Oppression
Authors: Goforth Anisa N. , Pham Andy V.
Published: January 2023

The education and mental health professions are political and ideological activities that inherently involve ideals, power, and opportunity. This creates unavoidable conflict, particularly in school systems where biases, prejudice, and discrimination are likely to occur and escalate. Social justice is an aspiration that recognizes diversity and equity of social, economic, political, and educational rights through redistribution of resources, opportunities, and privilege, and through representation of diverse people, thoughts, and ideas. Promoting social justice requires cultivating cultural humility and establishing positive relationships with colleagues, families, and students who historically have been marginalized. It also requires our efforts, energy, and additional resources to create systems-level change. The chapter provides a cultural humility framework that can aid in promoting social justice at the individual and systemic levels.
Creating Positive Relationships with Children and Families
Authors: Goforth Anisa N. , Pham Andy V.
Published: January 2023

Partnerships between families and schools are crucial for children’s overall success in school. Engaging with families can be especially challenging when cultural differences are present. Ultimately, collaboration is the foundation needed for these partnerships to be authentic and successful. Healthy family–school relationships are built on trust, sensitivity, and equality. This chapter describes the elements necessary to form partnerships between schools and families, including engaging in critical reflexivity, developing partnerships through trust and reciprocity, creating an action team, developing goals, and finally, implementing and evaluating the action plan. The connections that practitioners have with students and their families inspire them to continue the work they do, even when they might face challenges that naturally come with working in schools.
Cultural Perspectives of Mental Health and Traumatic Stress
Authors: Goforth Anisa N. , Pham Andy V.
Published: January 2023

The purpose of this chapter is to provide a culturally responsive framework for assessing students who experience difficulties related to mental health and traumatic stress. The chapter highlights the cultural perspectives of mental health and traumatic stress. One such perspective is considering how the construct of mental health or a “life well lived” is shaped by the values of our society. It is critical to consider these cultural factors, including expressions of distress and beliefs about help seeking, within a culturally responsive assessment. There are five steps within culturally responsive assessment: (1) engaging in critical reflexivity, (2) developing relationships and earning trust with the student and family, (3) obtaining background information, (4) conducting interviews with caregivers, (4) administering tests and measures, and (5) providing written and oral feedback to the student and caregivers.
The Couple as “Client”
Authors: Starks Tyrel J.
Published: January 2023

This chapter outlines core concepts of interdependence theory and describes their application to Motivational Interviewing with couples. Dependence is defined as a state in which partners are reliant on one another to achieve desired outcomes. In such situations, when partners’ preferences, priorities, or goals conflict, those in high-functioning relationships have relatively more motivation to set aside a focus on personal gains to consider the consequences of their actions for their partner and the relationship as a whole. This transformation of motivation increases the likelihood of adaptive accommodation responses that minimize conflict and create the opportunity to negotiate consensus or joint goals in which both partners have an investment. The process of facilitating dyadic functioning and techniques such as dyadic reflections and relationship affirmations therefore emerge as novel mechanisms by which the counselor can catalyze the couples’ capacity to identify and work toward shared goals for change.
Session 1: Trichotillomania (TTM) Education, Therapy Overview, Expectations, and Assessment of Pulling Triggers
Authors: Woods Douglas W. , Twohig Michael P.
Published: January 2023

This chapter introduces trichotillomania, which is chronic hair pulling resulting in noticeable hair loss. Scalp hair, eyebrows, and beards are some of the common hair-pulling areas. People diagnosed with trichotillomania experience substantial distress or impairment in important areas of their life. They tend to feel an increasing sense of tension immediately before pulling out the hair and when trying to resist pulling and feel a sense of gratification when pulling hair. Some people tend to use automatic hair pulling, which occurs when hairs are pulled outside of the person’s awareness, while others use focused hair pulling to control private experiences like urges, sensations, thoughts, or emotions. The chapter discusses how trichotillomania can be treated through habit reversal training and trigger reduction procedures and offers ways of self-monitoring trichotillomania.
Session 2: Habit Reversal Training (HRT) and Trigger Reduction Strategies
Authors: Woods Douglas W. , Twohig Michael P.
Published: January 2023

This chapter focuses on habit reversal training (HRT) and trigger reduction strategies for trichotillomania. Habit reversal training helps the patient to stop pulling hair through awareness training and competing response training. Awareness training requires the patient to describe the sensations and behaviors that precede pulling. Competing responses are used to make it physically impossible for the patient to pull their hair. They must be easy to perform and not noticeable. The chapter discusses ways to reduce the triggers to pull in varying environments, such as bathrooms and bedrooms and while playing video games. Trigger reduction strategies should be simple, should make pulling more difficult, and should not be used to avoid uncomfortable experiences.
Session 1: Trichotillomania (TTM) Education, Therapy Overview, Expectations, and Assessment of Pulling Triggers
Authors: Woods Douglas W. , Twohig Michael P.
Published: January 2023

This chapter outlines the first session of the Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T). It highlights the purpose of psychoeducation, which is to make sure the client has a basic understanding of trichotillomania (TTM) and knows they are not alone in experiencing the disorder. Clients with TTM often have urges to pull, feel pressure in pulling sites, and experience both pleasure and anger from their pulling. Clients are taught that pulling is a complicated action made up of individual and powerful factors. Clients are introduced to the weekly self-assessments of pulling that they will be asked to complete throughout treatment.