bluuebunny/crossref_metadata_2025 huggingface dataset:
PREDICTORS AND OUTCOMES OF BIOLOGIC/IMMUNOSUPPRESSIVE THERAPY FOR PSC-ASSOCIATED IBD
Authors: Sayed Amr , Silveira Marina , Assis David , Deng Yanhong , Gaidos Jill , Proctor Deborah , Al-Bawardy Badr
Published: January 2022

BACKGROUND

Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). PSC-IBD tends to be mild and responsive to mesalamine in most patients. However, some may require immunosuppressive (IMM) or biologic therapy to treat PSC-IBD. The aims of this study are to investigate the rates, predictors, and outcomes of biologic/IMM treatment of PSC-IBD.

METHODS

This was a single center, retrospective study of patients with PSC from 1/1/2012 to 4/1/2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of biologic/IMM therapy to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission (per physician global assessment), endoscopic healing (absence of ulcers/erosions) in patients who required biologics/IMM. Patients who required biologics or IMM to treat PSC-IBD (biologic/IMM group) were compared to patients who did not require biologics/IMM. Continuous variables were compared using an unpaired Student’s t-test. Categorical variables were compared using a Chi-square or Fisher’s Exact test as appropriate.

RESULTS

A total of 106 patients with PSC were reviewed and 72 (68%) had confirmed PSC-IBD and were included in the study. The median age was 48 years (IQR 33-59.5) and 69.4% were male (Table 1). A total of 22 patients (30.6%) required biologic/small molecule therapy (infliximab in 6; ustekinumab in 6; vedolizumab in 5; adalimumab in 4; tofacitinib in 1) and 6 (8.3%) needed thiopurine monotherapy to treat PSC-IBD. Overall, 28 patients (38.9%) required biologics/IMM to treat PSC-IBD. In the biologics/IMM group, 9 patients (32.1%) had small bowel involvement compared to 2 patients (4.6%) who did not require biologic/IMM (p=0.002). In the biologic/IMM group, 7 (25%) had overlap autoimmune hepatitis (AIH) compared to 3 (6.8%) in patients who did not require biologic/IMM for PSC-IBD (p=0.04). In the biologic/IMM group, 18 (64.3%) subjects were also treated with ursodeoxycholic acid (UDCA) compared to 29 (65.9%) in the non-biologic/IMM group (p=0.89). At least 1 episode of cholangitis was noted in 12 patients (42.9%) in the biologic/IMM group compared to 14 (31.8%) in the non-biologic/IMM group (p=0.34). In the biologic/IMM group, clinical remission was achieved in 22 patients (78.6%) but endoscopic healing in only 14 (50%).

CONCLUSIONS

In our cohort, up to a third of patients with PSC-IBD required biologics/IMM. Small bowel involvement was associated with the need for biologic/IMM. The use of biologic/IMM resulted in clinical remission in over three quarters of the PSC-IBD subjects however endoscopic healing was only achieved in half. The use of biologics/IMM was not associated with a higher rate of cholangitis but larger studies are needed to investigate the effects of different biologic classes on outcomes.
CROHN’S DISEASE COMPLICATED BY ILEOSIGMOID FISTULA: ASSESSMENT AND MANAGEMENT UPDATE
Authors: Benammi Sarah , Calini Giacomo , Abdalla Solafah , Mathis Kellie
Published: January 2022

BACKGROUND

The preoperative evaluation of Crohn’s-related ileosigmoid fistula (ISF) is complex with multiple preoperative diagnostic modalities available. Intraoperative management is also complicated when deciding whether to repair the fistula or resect the involved sigmoid. How these choices impact outcomes is not clear. We aim to evaluate the impact of sigmoid resection versus conservative fistula repair on postoperative complications when treating ISF.

METHODS

Patients with Crohn’s disease (CD) undergoing ileocolic resection in the setting of an ISF between January 1, 2007 and December 31, 2017 were identified. A retrospective chart review was conducted to collect data on preoperative workup, intra-operative technique, and 30-day complications. Intra-abdominal sepsis was defined as the presence of an intra-abdominal abscess or anastomotic leak from the sigmoid colon postoperatively. Univariate comparisons were performed between those undergoing primary repair versus sigmoid resection with primary anastomosis.

RESULTS

61 patients (62.3% female) with a median age of 37 years (range, 18-73)were included. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) each had a sensitivity of 100% versus 42% sensitivity for colonoscopy. When accounting for pre-operative endoscopy results, patients with endoscopic sigmoidal mucosal CD more often underwent sigmoid resection than patients with a normal sigmoidal mucosa or only a solitary fistulous opening in the sigmoid colon (p<0.001). When comparing primary repair vs sigmoid resection there was no difference in the occurrence of intra-abdominal septic complications (p=0.342) or anastomotic leak complication (p=0.239).

CONCLUSION

In summary, our study shows that conservative repair of the fistula is a safe option. Appropriate patient assessment and preoperative identification of the fistula is critical so that the management strategies for ISF and the potential implications can be discussed with the patient. CTE and MRE are the modalities of choice to diagnose ISF, while colonoscopy has a role in staging the burden of mucosal disease in the sigmoid colon. These tests help guide surgical decision-making with respect to resection versus primary repair of the sigmoid colon and will allow patients in whom the sigmoid colon is an innocent bystander to undergo a less extensive operation.
IBD AND THE PATIENT-PROVIDER RELATIONSHIP: DOES TRUST IMPACT TELEMEDICINE UTILIZATION?
Authors: Katta Meghna , Shao Connie , Herbey Ivan , Modi Sagar , Gleason Lauren , Marques Isabel , Duong Teressa , Lopez Elizabeth , Hair Kaycee , Chu Daniel
Published: January 2022

BACKGROUND

Telemedicine use has increased during the COVID-19 pandemic, but uptake among patient populations has not been equitable. Lack of access to technology or broadband connection contributes to the digital divide, but additional factors at the provider-level may contribute. We aimed to identify barriers and facilitators to inflammatory bowel disease (IBD) patient use of telemedicine with a focus on trust and the patient-provider relationship.

METHODS

Patients 18 years and older who were seen via telemedicine at a colorectal surgery clinic at a high-volume, tertiary care academic center were contacted for participation in this study. Patient demographics including age at surgery, race, sex, and diagnosis were recorded. Patient health literacy was evaluated using the BRIEF Health Literacy Screening Tool. The Wake Forest Physician Trust Scale (WFPTS) was used to measure patient trust in providers. Individual semi-structured interviews based on developed guides explored barriers and facilitators to telemedicine use. NVivo12 software was used for qualitative analysis and data organization. Coders reviewed each transcript independently, convening after initial review for discussion. Final themes were analyzed by disease process.

RESULTS

Among 29 participants, 24% of patients underwent colorectal surgery for treatment of IBD. 52% identified as female, 67% White, 30% Black, and 4% Latino, which closely mirrors the racial demographics of the study region. 33.3% of patients had limited health literacy (BRIEF score < 17) with an overall mean BRIEF score of 17.6 out of 20 (SD 3.33). The WFPTS scale ranged from 44 to 50, with a mean of 48.5 (SD 2.1) in IBD patients. Among IBD patients, three major themes were identified as important with respect to trust during telemedicine visits: trust in providers, trust in the institution, and trust in the surgical process. Of these, provider-level trust appeared to most influence patient trust in telemedicine. All participants noted that surgeon confidence and reputation affected trust in telemedicine. In the majority of IBD patients, a surgery referral from a trusted provider was an important factor in a patient’s trust and utilization of telemedicine pre and post operatively. Additionally, the duration of the patient encounter, pre-operative education, and the surgeon’s ability to answer questions appeared most relevant to IBD patients.

LIMITATIONS

The generalizability of our results may be limited because all patients were seen via telemedicine at a single institution.

CONCLUSION

Provider-level trust may have an increased role in IBD patients. To improve patient trust and telemedicine engagement in the IBD patient population, providers and healthcare systems should build and integrate interventions that enhance communication and interpersonal skills.
IMPLICATIONS OF ADOLESCENT AND PARENT PERCIEVED SKILL-BUILDING ON MISCARREID HELPING AND SELF-EFFICACY FOLLOWING A TRANSITION WORKSHOP FOR ADOLESCENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Waschmann Malika , Lin Henry , Stellway Jacklyn
Published: January 2022

BACKGROUND

The rising prevalence of Inflammatory Bowel Disease (IBD) in children and subsequent need for continued care into adulthood, begets the call for patient education on the transition to adult healthcare. To address this need, we designed a virtual, transition program for adolescents with IBD and their parents. The objective of this study was to assess program efficacy by examining changes in transition readiness skills, self-efficacy, and miscarried helping.

METHODS

Sixteen adolescent-parent dyads participated in the transition workshop. The program was structured around the biopsychosocial model of health and a multidisciplinary group of professionals contributed. The impact of the workshop was measured by validated self- and parent-report measures of transition readiness (transition readiness assessment questionnaire; TRAQ), self-efficacy (IBD-self efficacy scale; IBD-SES), and miscarried helping (Helping for Health Inventory; HHI) at pre-workshop and 1-year post-workshop. Median values were used to perform Wilcoxon rank sum tests and Spearman correlations for statistical analysis.

RESULTS

Adolescents gained tangible transition readiness skills as demonstrated by improvement in self- and parent-reported TRAQ scores at 12 months (median increase of 14 points and 19 points respectively, p<0.05). Parents reported less miscarried helping as demonstrated by improved HHI scores, however, adolescents did not (median decrease of 2 points). Adolescent IBD-SES scores improved at 12 months (median increase of 1 point). There was weak correlation between: 1) Adolescent IBD-SES and TRAQ scores (r=0.42), and 2) Parent TRAQ and HHI scores (r=0.49).

DISCUSSION/CONCLUSIONS

Improvements in adolescent TRAQ scores indicate that following the workshop, participants more frequently performed tasks necessary to manage their disease. Improvement in parent-reported TRAQ scores suggest parents also witnessed their child taking on more responsibility and developing autonomy. Correlation between improved parent-reported TRAQ scores and improved HHI scores suggests that as adolescents gain more autonomy over the day-to-day tasks of managing their IBD, their parents more readily allow them to take the lead, but the weak correlation observed could be from the small sample size given the attrition in survey response rate at 12 months. The correlation between increased adolescent TRAQ scores and IBD-SES scores suggest that as adolescents engage in disease management tasks they develop increased self-efficacy in relation to their disease as a delayed measure of program success. Future directions include implementing more frequent topic-based workshops to allow for peer-to-peer learning and increasing our sample size to increase the power of our analysis.
SECURE ELECTRONIC DOCUMENT SIGNING UPTAKE IN BIOLOGIC PRESCRIBING FOR IMMUNE MEDIATED DISEASES
Authors: Sharma Sowmya , Jones Jennifer , Stewart Michael
Published: January 2022

BACKGROUND

The COVID-19 pandemic drastically impacted workflows in gastroenterology practice. Physicians managing immune-mediated diseases (IMDs) must complete special authorization (SA) and prescription renewal (Rx) forms for patients on biologic therapy. This adds significant administrative burden potentially leading to delays in therapy initiation and care continuity. Historically, document completion has largely been paper-based, with forms faxed between patient support programs (PSPs) and physician offices. Disruption of normal office processes during the pandemic necessitated the movement of existing paper-based workflows online. The use of secure electronic document signing (SEDS) platforms has allowed physicians to receive and complete documents digitally.

AIMS

To evaluate the impact of SEDS-based biologic documentation on clinical practice. Objectives were 1) to determine if the use of SEDS platforms increased timeliness of document returns compared to traditional workflows 2) assess whether SEDS usage is acceptable and sustainable and 3) assess MD satisfaction with SEDS platforms.

METHODS

This was a retrospective audit of SEDS and paper-based biologic document workflows from a single PSP (Abbvie Care). Outcomes of interest were the number of documents completed monthly using SEDS, new monthly users, and the number of active monthly users between April 1, 2020-March 31, 2021. Time (days) to SEDS completion (vs. paper process) was determined by reviewing timepoint data for SA and Rx documents from May 2019-January 2020 (‘pre- SEDS’) and for SEDS documents from May 2020-January 2021(‘SEDS’). The return time (RT) was defined as the time between date sent to a physician’s office by the PSP to the date returned to the PSP. Documents in the pre-SEDS cohort with a RT exceeding 30 days were excluded

RESULTS

In totally, 5573 SA and Rx documents were completed by 383 physicians using the SEDS platform from April 2020-March 2021. A mean of 14.6 (sd 21.8) documents were signed per physician. The number of monthly electronic documents processed increased from 104 in April 2020 to 800 in March 2021. Active monthly users increased from 24 in April 2020 to 213 in March 2021 (31 new users monthly). A total of 19,387 paper documents were processed during the ‘pre-SEDS’ period and 3,317 electronic documents processed in the ‘SEDS’ period. The mean RT in the ‘pre-SEDS’ period was 8.03 days (Sd 8.2) and the ‘SEDS’ period was 1.11 days (sd 2.6).

CONCLUSION

This data demonstrates acceptability, appropriateness, and improved processing efficiency of an SEDS platform improving timeliness of patient care. Next steps in this research include surveying physicians to understand the work-flow impact of SEDS, functionality, long-term sustainability, satisfaction and impacts on disease related outcomes.
PEOPLE WITH IBD WANT TO TALK ABOUT SLEEP: RECOMMENDATIONS ON WHAT TO ASK AND HOW TO RESPOND TO SLEEP COMPLAINTS
Authors: Salwen-Deremer Jessica , Jagielski Christina , Smith Michael , Siegel Corey
Published: January 2022

BACKGROUND

Poor sleep occurs in 75% of people with IBD and is prospectively associated with increased risk for disease flare, hospitalization, surgery, and reduced quality of life. While IBD providers know the link between poor sleep and IBD, few are adequately armed to ask patients about sleep and provide concise, evidence based suggestions for management. We aimed to understand patients’ beliefs about sleep and IBD, their treatment preferences, and offer recommendations to providers on how best to ask about and address sleep problems in this population.

METHOD

We conducted an anonymous, online survey of 312 adults with Crohn’s disease or ulcerative colitis who sought treatment at the Dartmouth-Hitchcock IBD center. Participants were asked about sleep patterns, thoughts and behaviors related to sleep, and open-ended questions about sleep and IBD.

RESULTS

Participants ranged from 18-85 years old (M=48.6, SD=16.1) and were 66% women, 96% White. 61% of participants had Crohn’s and 39% had UC; mean symptom duration=20.7 years (SD=13.7). Overall, 81% of participants endorsed some interaction between sleep and IBD. Based on thematic analysis, participants thought that their sleep was worse during flares and sleeping poorly made IBD symptoms worse, while good sleep was protective. Pain, nighttime bowel movements, and general and IBD-specific anxiety all worsened sleep. Participants with poor sleep evidenced more dysfunctional beliefs about sleep (d=1.68, p<.001). They also were more likely to engage in behaviors that can worsen sleep, including taking daytime naps (d=1.16, p=.03), lying in bed while in pain during the day (d=1.19, p<.001), and worrying/planning in bed (d=.99, p<.001). 70% of participants thought that IBD providers should ask about sleep during visits and 67% of those with poor sleep thought IBD providers should provide sleep recommendations. 83% of people with poor sleep were interested in sleep treatment and/or information, provided it was not time intensive. Access to treatment, availability, cost, lack of knowledge about treatment options, and disinterest in medication were all major barriers to seeking treatment.

CONCLUSIONS

People with IBD believe there is a link between sleep and IBD and may be engaging in thought and behavior patterns that worsen sleep, and, likely, their IBD. While access to behavioral sleep medicine specialists can be limited, patients are quite receptive to getting sleep information from their IBD providers. To address these patient needs, providers may ask about weekday/weekend sleep differences and what patients do in bed besides sleep. Patients should be encouraged to maintain consistent sleep/wake times, not take naps (or nap for 20-30 minutes before lunch), use their beds only for sleep and sex, and not spend time in bed when they are not sleeping (e.g., if resting when fatigued or in pain).
THE CROHN’S AND COLITIS DISTRESS SCALE: ASSESSING THE DOMAINS OF IMPACT IN YOUTH WITH IBD
Authors: Cummings Caroline , Stellway Jacklyn , Paternostro Jennifer , Stoeckel Maggie , Muir Linda , Harris Michael
Published: January 2022

INTRODUCTION

Youth with Inflammatory Bowel Disease (IBD) are at significantly increased risk for depression and anxiety, with 25%-40% of youth with IBD reporting internalizing symptoms. These data are based on general measures of anxiety and depression without accounting for the confounds of disease-related processes. Disease-distress, on the other hand, disentangles disease-related processes, including medication sides effects, and the emotional experience of managing a chronic illness. Harris et al. developed a measure of IBD-related distress, the Crohn’s and Colitis Distress Scale (CCDS), to assess the expected worries, concerns, and fears associated with having IBD. This study involved an exploratory factor analysis (EFA) of the CCDS to better categorize IBD distress.

METHODS

Participants (N=120, ages 12-18, diagnosis of IBD) completed the 27-item CCDS. About half of participants were male (n=66; 55%) and majority were White (n=104; 86.7%). Eighty participants were diagnosed with Crohn’s disease (66.7%) and forty with ulcerative colitis (33.3%). Average length of time since diagnosis was 3.31 years (SD=2.77 years) and average length of time since participants’ last flare was 18.03 months (SD=24.65 months). A subsample of participants reported currently being symptomatic (n=44; 36.7%) and currently flaring (n=27; 22.5%). An EFA with varimax rotation was conducted to assess the factor structure of the CCDS.

RESULTS

The CCDS yielded a five-factor structure, with three to seven items per factor. Factor loadings ranged from .44 to .83 (see Table). Five factors were extracted from the EFA: emotional burden, physician-related, disease-related interpersonal, regimen-related, and disease-related functional impairment. An item-to-total analysis indicated 23 of 27 total items correlated strongly with the total (r > .5), four items were moderately correlated with the total (r= .43, r= .42, r= .38, and r= .49), and no items were largely uncorrelated with the total. Based on the factor analysis results, only items with an adequate factor loading, or were face valid or unique items for their respective factor domain, were retained. A final 22-item CCDS was supported.

CONCLUSIONS

The CCDS demonstrated a five-factor structure and the 22-item version was psychometrically sound. The factors that emerged are consistent with the disease-specific distress domains identified in other pediatric health populations (e.g., type 1 diabetes), as well as symptom-related distress as found in adults with IBD. Further validation of the measure is warranted, including assessment of the psychometric soundness of the regimen-related subscale. To our knowledge, the CCDS is the first multifaceted IBD-specific distress instrument to be developed for use with pediatric patients and may allow for further specificity in the identification of IBD-specific distress in this population.
Riding the Wave: Reactive Vector-Borne Disease Policy Renders the United States Vulnerable to Outbreaks and Insecticide Resistance
Authors: Dye-Braumuller Kyndall C , Gordon Jennifer R , McCoy Kaci , Johnson Danielle , Dinglasan Rhoel , Nolan Melissa S
Published: January 2022

Funding for vector-borne disease surveillance, management, and research is cyclical and reactive in the United States. The subsequent effects have yielded gross inequities nationally that unintentionally support recurrent outbreaks. This policy forum is comprised of four primary subsections that collectively identify specific areas for improvement and offer innovative solutions to address national inadequacies in vector borne disease policy and infrastructure.
Spatial Distribution of PCR-Identified Species ofAnopheles gambiae senu lato(Diptera: Culicidae) Across Three Eco-Vegetational Zones in Cross River State, Nigeria
Authors: Thabet H S , TagEldin R A , Fahmy N T , Diclaro J W , Alaribe A A , Ezedinachi E , Nwachuku N S , Odey F O , Arimoto H
Published: January 2022

Anopheles gambiae sensu lato complex (An. gambiae s.l.) describes a group of nine morphologically indistinguishable members that vary in their distribution, ability to transmit malaria, and susceptibility to pyrethroids. Here, we recorded the spatial patterns of PCR-identified An. gambiae s.l. complex species collected from four sites in Cross River State, Nigeria that represented three different ecological zones. Trapping was conducted between October 2015 and June 2016. Anopheles gambiae s.l. complex species identification was performed using species-specific primers followed by An. gambiae and An. coluzzii differentiation using the restriction fragment length polymorphism (RFLP) method. Bivariate and multivariate logistic regression models were used to identify ecological and seasonal variables closely associated with An. coluzzii and An. gambiae distribution. Out of 1,388 An. gambiae s.l. successfully amplified, 1,074 (77.4%) were An. coluzzii, 278 (20%) were An. gambiae, and 25 (1.8%) were hybrids (An. coluzzii/An. gambiae). A very small number of An. arabiensis (0.8%, n = 11) were also collected. Statistical analysis indicated that An. coluzzii is predominant in Guinea-savannah and tropical rainforest, and is highly associated with rainy seasons, while, An. gambiae is prevalent in mangrove swamp forest during dry seasons. Only 13 An. gambiae s.l. females were infected with Plasmodium falciparum (P. falciparum). The sporozoite infection rate was higher in mangrove swamp forest (53.8%, n = 7) than in rain forest (38.5%, n = 5) followed by Guinea-savannah (7.7%, n = 1) ecological zones. These results provide important insights for strategic planning of malaria control programs in Nigeria.
Perspectives on Cervical Arthroplasty in Navy and Marine Corps Tactical Jet Aircrew
Authors: Lang Richard W , Yoder Adam J , Porensky Paul
Published: January 2022

Symptomatic cervical spondylosis is a progressive degenerative condition of the cervical spine commonly resulting in functionally-limiting pain, weakness, and/or limited dexterity. Symptomatic cervical spondylosis is believed to occur at higher rates in military aviators than civilian counterparts and is a disqualifying condition for all Navy and Marine Corps aircrew. This condition is non-waiverable for tactical jet (ejection-seat-based) aviators. Medical attrition of experienced tactical jet aircrew from the military aviation community results in substantial cost to the U.S. Government, reduces fleet combat capability, and adversely impacts career progression and retention. The clinical maturation of cervical total disc replacement (TDR) technology over the last 2 decades has revolutionized the treatment of symptomatic cervical spondylosis and enabled a return to duty for hundreds of military service members in non-aviation fields. TDR studies demonstrate equal or superior functional outcomes, rates of symptom resolution, reduced complication and reoperation rates, and lower long-term cost compared to traditional Anterior Cervical Discectomy and Fusion (ACDF). Although initial computational modeling studies have evaluated cervical arthroplasty performance during rotary-wing crash impacts, safety within the dynamic tactical jet environment has not yet been established. The purpose of this article is to review factors relevant to TDR safety and outcomes and to propose a framework to evaluate the safety of TDR in Navy and Marine Corps tactical jet aircrew, to ultimately inform aeromedical algorithms regarding return to flight after TDR.
Associations Between Vancomycin Exposure and Acute Kidney Injury Within the Recommended Area Under the Curve Therapeutic Exposure Range Among Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infections
Authors: Lodise Thomas P , Scheetz Marc , Carreno Joseph J , Chambers Henry , Fowler Vance , Holland Thomas L
Published: January 2022

Among patients with methicillin-resistant Staphylococcus aureus bacteremia, vancomycin-associated acute kidney injury increased as a function of the day 2 area under the curve (AUC), even for daily AUCs within the recommended therapeutic range (400–600). Further data are needed to determine if daily AUCs <400 can be maintained without compromising efficacy.
Sustained Reduction in Urgent Care Antibiotic Prescribing During the Coronavirus Disease 2019 Pandemic: An Academic Medical Center’s Experience
Authors: Ha David , Ong’uti Sharon , Chang Amy , Mui Emily , Nelligan Ian , Betts Brooke , Lentz Christopher , Alegria William , Fox Emily , Meng Lina , Stenehjem Edward , Hersh Adam L , Deresinski Stanley , Artandi Maja , Holubar Marisa
Published: January 2022

We compared antibiotic prescribing before and during the ­coronavirus disease 2019 (COVID-19) pandemic at 2 academic urgent care clinics and found a sustained decrease in prescribing driven by respiratory encounters and despite transitioning to telemedicine. Antibiotics were rarely prescribed during encounters for COVID-19 or COVID-19 symptoms. COVID-19 revealed opportunities for outpatient stewardship programs.
Long-term policy impacts of the coronavirus: normalization, adaptation, and acceleration in the post-COVID state
Authors: Capano Giliberto , Howlett Michael , Jarvis Darryl S L , Ramesh M
Published: January 2022

This paper offers an analysis of the theoretical and empirical challenges the coronavirus pandemic poses for theories of policy change. Critical events like coronavirus disease are potentially powerful destabilizers that can trigger discontinuity in policy trajectories and thus are an opportunity for accentuating path shifts. In this paper, we argue that three dynamic pathways of change are possible and must be considered when analysing post-COVID policymaking: normalization, adaptation, and acceleration. These different pathways need to be explored in order to understand the mid- and long-term policy effects of the pandemic. This introduction contextualizes the articles in this special issue, situating them broadly within two broad categories: (a) assessment of how the coronavirus disease pandemic should be understood as a crisis event, and its role in relationship to mechanisms of policy change; and (b) mapping the future contours of the pandemic’s impact on substantive policy areas, including education, health care, public finance, social protection, population ageing, the future of work, and violence against women.
Heterosis and Combining Ability in Pumpkin Inbreds (Cucurbita moschataDuch. ex Poir.)
Authors: Shafin Most. Shaika , Parvin Most. Shanaj , Haque Md Ehsanul , Akhter Fahmida
Published: January 2022

Twenty hybrids along with five parents evaluated in the study were mainly contemplated to find out the best cross combinations and the best general and specific combiners as well as to estimate the nature and magnitude of the gene action for different qualitative traits. Using Griffing’s and Hayman’s approach through a 5 × 5 full diallel cross fashion, an investigation on heterosis and combining ability in pumpkin was undertaken following RCBD design with three replications at the experimental field. Both positive and negative significant GCA and SCA variances were obtained from few parents and hybrids. Predominance of additive-additive gene action was noted for most of the characters except hollowness and dry matter content, where additive-dominance gene action was predominant; flesh thickness and brix (%), where dominance-dominance gene action were predominant. A single parent was not found as good combiner for more than two characters. The best specific combiners were IBD 40 X IBD 47 for beta carotene, total sugar and fruit yield; IBD23 X IBD40 for brix (%), hollowness and flesh thickness; IBD40 X IBD57 for fruit breadth; IBD47 X IBD50 for non reducing sugar; and IBD47 X IBD57 for reducing sugar. The Vr-Wr graphs exhibited complete, partial and over dominance effect of genes for different characters. Complete dominance was observed only for beta carotene whereas over dominance was noticed for hollowness and flesh thickness. Partial dominance was ensured for fruit breadth, dry matter, brix (%), reducing sugar, non-reducing sugar, total sugar and fruit yield. Significant heterosis of some crosses against mid parent and better parents were observed for some characters.
Tissue-intrinsic γδ T cells critically regulate Tissue-Resident Memory CD8 T cells
Authors: Muñoz-Ruiz Miguel , Llorian Miriam , D’Antuono Rocco , Pavlova Anna , Mavrigiannaki Anna Maria , McKenzie Duncan , García-Cassani Bethania , Iannitto Maria Luisa , Jandke Anett , Ushakov Dmitry S. , Hayday Adrian C
Published: January 2022

Because Tissue-Resident Memory T (TRM) cells contribute critically to body-surface immunoprotection and/or immunopathology in multiple settings, their regulation is biologically and clinically important. Interestingly, TRMcommonly develop in epithelia part-shaped by innate-like lymphocytes that become tissue-intrinsic during development. Here we show that polyclonal TRMcells induced by allergic contact dermatitis (ACD) interact with signature intraepidermal γδ T cells, facilitating a feedback-loop wherein TRM-derived IFNγ upregulates PD-L1 on γδ cells that can thereupon regulate PD1+TRM. Thus, TRMinduced by ACD in mice lacking either local γδ cells, or lacking a single gene (IFNγR) expressed by local γδ cells, displayed enhanced proliferative and effector potentials. Those phenotypes were associated with strikingly limited motility, reduced TRMquality. and an impaired capacity to restrain melanoma. Thus, inter-individual and tissue-specific variation in how tissue-intrinsic lymphocytes integrate with TRMmay sit upstream of variation in responses to cancer, allergens and other challenges, and may likewise underpin inflammatory pathologies repeatedly observed in γδ-deficient animals.
Xeno-monitoring of molecular drivers of artemisinin and partner drug resistance in P. falciparum populations in malaria vectors across Cameroon
Authors: Nkemngo Francis N. , Mugenzi Leon M.J. , Tchouakui Magellan , Nguiffo-Nguete Daniel , Wondji Murielle J. , Mbakam Bertrand , Tchoupo Micareme , Ndo Cyrille , Wanji Samuel , Wondji Charles S.
Published: January 2022

Background

Monitoring of drug resistance in Plasmodium populations is crucial for malaria control. This has primarily been performed in humans and rarely in mosquitoes where parasites genetic recombination occurs. Here, we characterized the Plasmodium spp populations in wild Anopheles vectors by analyzing the genetic diversity of the P. falciparum kelch13 and mdr1 gene fragments implicated in artemisinin and partner drug resistance across Cameroon in three major malaria vectors.

Methods

Anopheles mosquitoes were collected across nine localities in Cameroon and dissected into the head/thorax (H/T) and abdomen (Abd) after species identification. A TaqMan assay was performed to detect Plasmodium infection. Fragments of the Kelch 13 and mdr1 genes were amplified in P. falciparum positive samples and directly sequenced to assess their drug resistance polymorphisms and genetic diversity profile.

Results

The study revealed a high Plasmodium infection rate in the major Anopheles vectors across Cameroon. Notably, An. funestus vector recorded the highest sporozoite (8.02%) and oocyst (14.41%) infection rates. A high P. falciparum sporozoite rate (80.08%) alongside epidemiological signatures of significant P. malariae (15.94%) circulation were recorded in these vectors. Low genetic diversity with six (A578S, R575I, G450R, L663L, G453D, N458D) and eight (H53H, V62L, V77E, N86Y, G102G, L132I, H143H, Y184F) point mutations were observed in the k13 and mdr1 backbones respectively. Remarkably, the R575I (4.44%) k13 and Y184F (64.2%) mdr1 mutations were the predominant variants in the P. falciparum populations.

Conclusion

The emerging signal of the R575I polymorphism in the Pfk13 propeller backbone entails the regular surveillance of molecular markers to inform evidence-based policy decisions. Moreover, the high frequency of the 86N184F allele highlights concerns on the plausible decline in efficacy of artemisinin-combination therapies (ACTs); further implying that parasite genotyping from mosquitoes can provide a more relevant scale for quantifying resistance epidemiology in the field.
Machine learning algorithms predict soil seed bank persistence from easily available traits
Authors: Rosbakh Sergey , Pichler Maximilian , Poschlod Peter
Published: January 2022

Question

Soil seed banks (SSB), i.e., pools of viable seeds in the soil and its surface, play a crucial role in plant biology and ecology. Information on seed persistence in soil is of great importance for fundamental and applied research, yet compiling datasets on this trait still requires enormous efforts. We asked whether the machine learning (ML) approach could be used to infer and predict SSB properties of a regional flora based on easily available data.

Location

Eighteen calcareous grasslands located along an elevational gradient of almost 2000 m in the Bavarian Alps, Germany.

Methods

We compared a commonly used ML model (random forest) with a conventional model (linear regression model) as to their ability to predict SSB presence/absence and density using empirical data on SSB characteristics (environmental, seed traits and phylogenetic predictors). Further, we identified the most important determinants of seed persistence in soil for predicting qualitative and quantitative SSB characteristics using the ML approach.

Results

We demonstrated that the ML model predicts SSB characteristics significantly better than the linear regression model. A single set of predictors (either environment, or seed traits, or phylogenetic eigenvectors) was sufficient for the ML model to achieve high performance in predicting SSB characteristics. Importantly, we established that a few widely available SSB predictors can achieve high predictive power in the ML approach, suggesting a high flexibility of the developed approach for use in various study systems.

Conclusions

Our study provides a novel methodological approach that combines empirical knowledge on the determinants of SSB characteristics with a modern, flexible statistical approach based on ML. It clearly demonstrates that ML can be developed into a key tool to facilitate labor-intensive, costly and time-consuming functional trait research.
Rice Pan-genome Array (RPGA): an efficient genotyping solution for pan-genome-based accelerated crop improvement in rice
Authors: Daware Anurag , Malik Ankit , Srivastava Rishi , Das Durdam , Ellur Ranjith K. , Singh Ashok K. , Tyagi Akhilesh K. , Parida Swarup K.
Published: January 2022

The advent of the pan-genome era has unraveled previously unknown genetic variation existing within diverse crop plants including rice. This untapped genetic variation is believed to account for a major portion of phenotypic variation existing in crop plants and might be responsible for missing heritability. However, the use of conventional single reference-guided genotyping often fails to capture large portion of this genetic variation leading to a reference bias. This makes it difficult to identify and utilize novel population/cultivar-specific genes for crop improvement. To overcome this challenge, we developed a rice pan-genome genotyping array (RPGA) includes 80K genome-wide SNPs which provides simple, user-friendly and cost-effective solution for rapid pan-genome-based genotyping in rice. The GWAS conducted using RPGA-SNP genotyping data of a rice diversity panel detected total of 42 loci, including previously known as well as novel genomic loci regulating grain size/weight traits in rice. Eight of the identified trait-associated loci (dispensable loci) could not be detected with conventional single reference genome-based GWAS and found to be missing from the commonly used Nipponbare reference genome. WD repeat-containing PROTEIN 12 gene underlying one of such dispensable locus on chromosome 7 (qLWR7) along with few other non-dispensable loci was subsequently detected using high-resolution QTL mapping confirming authenticity of RPGA-led GWAS. This demonstrates the potential of RPGA-based genotyping to overcome reference bias. Besides GWAS, the application of RPGA-based genotyping for natural allelic diversity and population structure analysis, seed purity and hybridity testing, ultra-high-density genetic map construction and chromosome level genome assembly, and marker-assisted foreground/background selection was successfully demonstrated. Based on these salient outcomes, a web application (http://www.rpgaweb.com) was also developed to provide easy to use platform for imputation of RPGA-based genotyping data using 3K Rice Reference Panel and subsequent GWAS in order to drive genetic improvement of rice.
Tracking the dynamics of perisaccadic visual signals with magnetoencephalography
Authors: Nasiotis Konstantinos , Neupane Sujaya , Bakhtiari Shahab , Baillet Sylvain , Pack Christopher C.
Published: January 2022

Many brain functions are difficult to localize, as they involve distributed networks that reconfigure themselves on short timescales. One example is the integration of oculomotor and visual signals that occurs with each eye movement: The brain must combine motor signals about the eye displacement with retinal signals, to infer the structure of the surrounding environment. Our understanding of this process comes primarily from single-neuron recordings, which are limited in spatial extent, or fMRI measurements, which have poor temporal resolution. We have therefore studied visual processing during eye movements, using magnetoencephalography (MEG), which affords high spatiotemporal resolution. Human subjects performed a task in which they reported the orientation of a visual stimulus while executing a saccade. After removal of eye movement artifacts, time-frequency analysis revealed a signal that propagated in the beta-frequency band from parietal cortex to visual cortex. This signal had the characteristics of perisaccadic “remapping”, a neural signature of the integration of oculomotor and visual signals. These results reveal a novel mechanism of visual perception and demonstrate that MEG can provide a useful window into distributed brain functions.
Actin networks modulate heterogenous NF-κB dynamics in response to TNFα
Authors: Butera Francesca , Sero Julia E. , Dent Lucas G. , Bakal Chris
Published: January 2022

The canonical NF-κB transcription factor RELA is a master regulator of immune and stress responses and is upregulated in PDAC tumours. Here, we characterised previously unknown endogenous RELA-GFP dynamics in PDAC cell lines by live single cell imaging, which revealed rapid, sustained and non-oscillatory nuclear RELA following TNFα stimulation. Using Bayesian analysis of single cell datasets with variation in nuclear RELA, we computationally predicted that RELA heterogeneity in PDAC cell lines is dependent on F-actin dynamics. By RNA-seq, we identified the actin regulators NUAK2 and ARHGAP31 as transcriptionally regulated by RELA. In turn,NUAK2orARHGAP31siRNA depletion downregulates TNFα-stimulated RELA nuclear localisation in PDAC cells, establishing a novel negative feedback loop regulating RELA activation by TNFα. We identify an additional actin-independent feedback loop involving RELB, which suppresses TNFα-mediated RELA nuclear localisation following RELA mediated upregulation of RELB. Taken together, we provide computational and experimental support for interdependence between the F-actin network and RELA translocation dynamics in PDAC.
Spatially Aware Dimension Reduction for Spatial Transcriptomics
Authors: Shang Lulu , Zhou Xiang
Published: January 2022

Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with enriched biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored and novel analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for spatial domain detection and explores its utility for trajectory inference on the tissue and for high-resolution spatial map construction. In the real data applications, SpatialPCA identifies key molecular and immunological signatures in a newly detected tumor surrounding microenvironment, including a tertiary lymphoid structure that shapes the gradual transcriptomic transition during tumorigenesis and metastasis. In addition, SpatialPCA detects the past neuronal developmental history that underlies the current transcriptomic landscape across tissue locations in the cortex.
Reduced feedback barely slows down proprioceptive recalibration
Authors: Ruttle Jennifer E. , Hart Bernard Marius ’t , Henriques Denise Y. P.
Published: January 2022

Introducing altered visual feedback of the hand results in quick adaptation of reaching movements. And while this may be partly due to explicit strategies, our lab has shown that implicit changes like reach aftereffects and shift in estimates of the unseen hand, can also emerge and even saturate within a few training trials. The goal of the current study is to determine whether these rapid changes in unseen hand position that occur during classical visuomotor adaptation are diminished or slowed when feedback during training is reduced. We reduced feedback by either providing visual feedback only at the end of the reach (terminal feedback) or constraining hand movements to reduce efferent contribution (exposure). We measured changes as participants completed reaches with a 30° rotation, a −30° rotation and clamped visual feedback, with these two “impoverished” training conditions, along with classical visuomotor adaptation training, while continuously estimating their felt hand position. Classic continuous-cursor training produced exemplary learning curves and rapid and robust shifts in felt hand position. Training with terminal feedback slightly reduced the initial rate of change in overall adaptation and but not the magnitude of shifts in felt hand position. Finally using a robot to constrain and deviate hand movement direction, called exposure training, only delayed saturation of proprioceptive changes by a single trial and these changes were slightly smaller than those during classical training. Taken together, adaptation and shifts in felt hand position are a rapid and robust responses to sensory mismatches and are only slightly modulated when feedback is reduced. This means that, given a visuo-proprioceptive mismatch, the resulting shift in sense of limb position can contribute to movements from the start of adaptation.
mRNA expression explains metabolic and thermal physiology
Authors: Drown Melissa , Crawford Douglas , Oleksiak Margie
Published: January 2022

Quantifying mRNA expression, which is heritable and physiologically inducible, reveals biologically important networks and pathways underlying complex traits. Here, we quantify mRNA expression in Fundulus heteroclitus, a small teleost fish, among three populations acclimated to 12°C and 28°C and relate it to variation in six, complex, physiological traits (whole animal metabolism (WAM), critical thermal maximum (CTmax), and four substrate specific cardiac metabolic rates (CaM)). Although 366 heart mRNAs and 528 brain mRNAs had significant differential expression between the two acclimation temperatures, none of the mRNA acclimation responses were shared across all three populations in any tissue. Yet, within an acclimation temperature across all three populations, weighted gene co-expression network analyses show that mRNA expression patterns explained WAM, CTmax, and CaM trait variation. These analyses revealed 9 significant heart MEs (first principal component of module expression) and 4 significant brain MEs. Heart MEs explained variation in WAM, CTmax, and two of the four substrate specific cardiac metabolic rates at 12°C, and CTmax at 28C. In contrast, brain MEs explained CTmax and WAM at 28°C but not at 12°C. Combining MEs as multiple correlations, 82% of variation in WAM at 12°C was explained by four heart MEs, 80% of variation in fatty-acid CaM at 12°C was explained by three heart MEs, and 72% of variation in CTmax at 28°C was explained by three brain MEs. These MEs were enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) terms related to specific metabolic pathways, suggesting that they represent biologically relevant pathways. Together these data suggest that mRNA co-expression explains complex traits; moreover, physiological traits are more reliant on heart expression at 12°C and brain expression at 28°C.

Author Summary

Despite an abundance of genomic data, the molecular and genetic underpinnings of complex traits remain poorly understood. To better understand the molecular basis of complex traits, we used heart and brain mRNA expression to explain complex traits- physiological responses to temperature- in individuals collected from three saltmarsh fish (Fundulus heteroclitus) populations acclimated to 12°C and 28°C. We found that while physiological traits did not differ among populations, the mRNAs important for acclimation responses were >88% unique to a single population and differed between heart and brain tissues. We also found tissue specific co-expressed mRNAs that explain up to 82% of complex traits including whole animal metabolism, upper thermal tolerance, and substrate specific cardiac metabolism measured at 12°C or 28°C acclimation conditions. Notably, sets of co-expressed mRNAs related to these traits are enriched for molecular pathways affecting metabolism, giving insight into the molecular underpinnings of these traits.