bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing Normal and Disordered Growth
Authors: Butler Gary
Published: January 2022

Normal growth is a good marker of a child’s well-being. Growth takes place differently during infancy, childhood, or adolescence. Infantile growth is the most rapid period. Childhood growth is slower but with mini-growth spurts. Pubertal physical changes are linked to the rapid acceleration and deceleration of adolescent growth. Puberty is assessed by Tanner staging, but a simpler non-invasive system of the assessing the puberty phases (prepuberty, in puberty, and completing puberty) may be more helpful in daily practice. Weight is multicomponent and body mass index may be a more helpful evaluation tool. WHO growth charts are suitable for use from birth to 5 years as they reflect the true pathway of early growth. Thereafter, local, UK or NCHS charts may be suitable. Specialist charts are available for preterm infants and specific syndromes (e.g. Down, Turner, achondroplasia). Additional useful tools include mid-parental or target height calculation, adult height prediction possibly by bone age estimation.
Management of Gynaecomastia
Authors: Braunstein Glenn D.
Published: January 2022

Gynaecomastia, the benign enlargement of the breast glandular tissue in a male, is a common clinical condition, caused in most instances by an imbalance between the breast stimulatory effects of oestrogen and the inhibitory effects of androgens. It is a normal physiological process in infancy, puberty, and senescence. A number of medications have been associated with gynaecomastia, as has several pathological conditions leading to increased oestrogen action or decreased androgen action. Gynaecomastia should be distinguished from pseudogynaecomastia, representing breast enlargement due to fat deposition and not glandular enlargement, and breast cancer through a careful breast examination. The cause of gynaecomastia may be elucidated through the history, general physical examination, and a few laboratory tests. Treating an underlying pathologic cause may lead to resolution of the gynaecomastia, especially if it is of short duration (less than 6 months). Otherwise, a trial of an antioestrogen such as tamoxifen may decrease pain, tenderness, and breast enlargement. Tamoxifen or breast radiotherapy may be used to prevent the development of gynaecomastia in men receiving hormonal therapy for prostate cancer. For chronic fibrotic gynaecomastia or gynaecomastia unresponsive to medical therapy or failing to spontaneously resolve over time, plastic surgical removal can give acceptable cosmetic results.
Long-Term Endocrine Sequalae of Cancer Therapy
Authors: Higham Claire E. , Murray Robert D.
Published: January 2022

There are an increasing number of patients living with and beyond cancer (LWBC) who are susceptible to both short- and long-term cancer therapy related side effects. Long-term endocrine sequelae of cancer therapies occur in up to 50% of childhood cancer survivors and may occur decades after the treatment has been delivered. These consequences of treatment can cause significant morbidity and increased mortality if not diagnosed and appropriately managed. This chapter will provide an overview of these endocrine sequalae include disturbances of growth and puberty, hypothalamo-pituitary (HP) dysfunction, hypogonadism, thyroid dysfunction, benign and malignant thyroid nodules, hyperparathyroidism, and bone effects. The relative contributions of cancer treatment modalities such as radiotherapy and chemotherapy and patient factors are discussed. Appropriate screening, diagnostic testing, and treatment algorithms are also described.
Medical Complications of Obesity
Authors: Jassil Friedrich C. , Batterham Rachel L.
Published: January 2022

Obesity is a chronic progressive condition. It is associated with adverse health outcomes affecting the cardiovascular, endocrine, gastrointestinal, urinary, respiratory, nervous, musculoskeletal, and reproductive systems. Obesity also increases the risk of certain malignancies and psychological comorbidities. The aetiopathogenesis of obesity-linked diseases is complex and not yet fully elucidated, however, clinical and experimental observations, as well as epidemiological studies, have identified a key role for adipocyte-derived factors, in particular from visceral adipose tissue and ectopic lipid deposition. These factors drive low-grade chronic systemic inflammation and mediate the development of at least some obesity-associated diseases. Increasing understanding of the mechanisms whereby obesity leads to a myriad of complications is urgently required to pave the way for development of novel evidence-based preventative and therapeutic strategies.
Hyperinsulinaemic Hypoglycaemia
Authors: Hussain Khalid , Galcheva Sonya
Published: January 2022

In hyperinsulinaemic hypoglycaemia (HH) insulin secretion is dysregulated so that insulin secretion persists in the presence of low blood glucose concentration. HH is a common cause of severe and persistent hypoglycaemia in neonates and children and early diagnosis is essential to avoid hypoglycaemic brain injury. Mutations in 14 different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1, PPM2, CACNA1D, FOXA2) have been linked to congenital forms of HH. Histologically, congenital HH can be divided into two main types namely diffuse and focal. Accessibility of rapid molecular genetic testing, pancreatic imaging with 18F-DOPA PET/CT and the availability of novel medical therapies has changed the clinical approach to patients with HH.
Haemochromatosis and Other Inherited Diseases of Iron Metabolism
Authors: Deugnier Yves , Bardou-Jacquet Edouard
Published: January 2022

Haemochromatosis was described centuries ago, yet the biological mechanisms involved were delineated only recently. Mutation in genes involved in iron metabolism (HFE in the most frequent form) leads to systemic iron overload which particularly affect the liver, pancreas, heart, joints, and pituitary. This can lead to cirrhosis, hepatocellular carcinoma, diabetes, heart failure, hypogonadism, and arthropathy. The diagnosis now relies on definite genetic testing, allowing earlier diagnosis and family screening. This chapter looks at how this lifelong treatment is based on bloodletting to normalize body iron stores and, provided it is initiated before the onset of massive iron overload, allows a normal life expectancy.
The Porphyrias
Authors: Badminton Michael N. , Schulenburg-Brand Danja
Published: January 2022

The porphyrias are a group of mainly inherited metabolic conditions resulting from partial deficiency, or in one condition increased activity, of individual enzymes of haem biosynthesis. Clinical presentation is either with acute neurovisceral attacks, skin photosensitivity, or both, due to overproduction of pathway intermediates. Diagnosis is based on biochemical testing, preferably during or soon after symptomatic periods. Penetrance in autosomal dominant acute porphyrias is low. They predominantly affect adult females and are managed by treatment of acute symptoms and intravenous haematin to suppress hepatic overproduction of precursors. Cutaneous porphyrias present in two distinct patterns of skin photosensitivity; acute painful photosensitivity (protoporphyrias) and fragile skin (bullous porphyrias). Treatment includes photoprotection against visible light (sunlight) especially for the erythropoietic porphyrias. Porphyria cutanea tarda (PCT) may be the first manifestation of liver disease and skin lesions can be effectively treated.
Presentation and Natural History of Type 1 Diabetes
Authors: Brooks Augustin
Published: January 2022

Type 1 diabetes results from loss of pancreatic β-cell function, producing a state of insulin insufficiency that results in spontaneous hyperglycaemia and ketone formation. Genetically susceptible individuals are believed to encounter an (as yet undefined) environmental trigger which initiates an autoimmune process, leading to autoantibody formation, activation of autoreactive T-lymphocytes and pancreatic β-cell destruction. Onset occurs at any age beyond 6 months, with two peak incidences at 5–7 years and during puberty. Incidence is increasing by 3–4% per year, implying a causative role for non-genetic factors. Symptomatic onset with polyuria, polydipsia, and weight loss later leads to presentation with diabetic ketoacidosis if untreated. The discovery of insulin transformed type 1 diabetes from a terminal disease to a manageable medical condition, although exogenous insulin replacement cannot fully mimic the natural regulatory ability of β-cells. Microvascular and macrovascular complications of chronically elevated glucose continue to cause premature morbidity and mortality, with mean reduction in life expectancy estimated at 11–13 years.
Pathogenesis
Authors: Walker Mark , Yu Xuefei , Gastaldelli Amalia
Published: January 2022

Type 2 diabetes is characterized by chronic hyperglycaemia. This results from decreased pancreatic beta-cell function and impaired insulin action, together with raised circulating glucagon levels and changes in the entero-insular axis. Headway is being made to define the mechanisms that underlie these pathophysiological changes. The combined effects of common but functionally weak genetic susceptibility variants constitute the major genetic predisposition to type 2 diabetes. While the majority of the genetic variants are related to altered insulin secretion, a proportion influence insulin action by altering adipose tissue distribution. At the cellular level, mechanisms are emerging that are common across the different tissues, including ectopic fat deposition and lipotoxicity, and the activation of pro-inflammatory pathways. The metabolic derangement in type 2 diabetes extends to altered lipid metabolism and the development of non-alcoholic fatty liver disease. Understanding the mechanisms that lead to type 2 diabetes will inform the development of future therapies.
Diagnosis of Non Type 1, Non Type 2 Forms of Diabetes
Authors: Owen Katharine R.
Published: January 2022

Diabetes that is neither type 1 nor type 2 in aetiology accounts for around 5% of cases, with a wide range of causes. The widest differential diagnosis is in the young adult group. Non-type 1/type 2 diabetes includes monogenic causes of both beta-cell dysfunction (MODY, neonatal diabetes, mitochondrial diabetes) and insulin resistance (lipodystrophy, insulin receptor defects and monogenic obesity), as well as pancreatic, endocrine, and syndromic causes. It is important to make the correct aetiological diagnosis as this is likely to affect treatment and other aspects of management as well as defining the risk of diabetes in family members. Apart from clinical features and basic biochemistry, there are a number of investigations which can help with determining aetiology. These include beta-cell antibodies, assessment of endogenous insulin secretion using C-peptide, specific biomarkers, and genetic testing. Combining some of these features has led to the development of an online probability model for MODY. It is important to understand the roles and limitations of these tests and tools in clinical practice.
Structured Education
Authors: Heller Simon , Elliott Jackie
Published: January 2022

Structured education is essential to successful diabetes self-management. In type 1 diabetes it provides patients and their families with the complex skills needed to maintain glucose levels close to normal while reducing the risk of hypoglycaemia and improving quality of life. In type 2 diabetes it can motivate individuals to make major lifestyle changes, enabling them to reach treatment goals with little or no medication. Even for those who struggle to lose weight or increase physical activity, increased understanding helps them to work collaboratively with health professionals in agreeing a joint management plan. Despite this, provision and particularly uptake of education programmes remains disappointingly low. Implementation of structured education demands enthusiastic support of professionals to commission high quality programmes meeting national and international standards. Such a policy is not expensive; economic analyses continue to demonstrate value for money and are dwarfed by the vast sums currently spent on diabetic complications.
Insulins and Insulin Delivery Devices
Authors: Choudhary Pratik , Jacob Peter
Published: January 2022

Insulin is the life-saving treatment in type 1 diabetes, and increasingly used to treat advanced type 2 diabetes. Over the years there have been improvements and alterations in insulin treatment, moving from animal-derived insulin, through recombinant human insulin to genetically modified analogue insulins to help support people with diabetes to achieve better glucose control. Improved insulin delivery through insulin pens and more complex devices such as insulin pumps have helped improve quality of life and biomedical outcomes such as lower HbA1c and reduced hypoglycaemia. In this chapter we will describe currently available insulins with a focus on clinical trials that demonstrate differences relevant to individual users. We go on to discuss the wide variety of devices used to administer these insulins together with a discussion of their relative advantages and disadvantages.
Type 2 Diabetes in Different Ethnic Groups
Authors: Gholap Nitin Narayan , Khunt Kamlesh
Published: January 2022

The prevalence of type 2 diabetes mellitus (T2DM) and its associated complications varies significantly between populations, with non-white ethnic populations, indigenous groups, and developing countries bearing a disproportionately higher burden of the disease. High-quality studies examining various aspects of T2DM and its management among diverse non-white ethnic groups remain limited. Furthermore, ethnic disparities in health may vary between countries due to various factors. However, existing evidence has identified common themes across these groups as being key contributors to their greater burden of disease. In the increasingly globalized world, healthcare professionals, and policymakers need to understand ethnic disparities in relation to T2DM and their determinants to provide effective care.
Diabetes Secondary to Pancreatic Disease
Authors: Weston Philip J.
Published: January 2022

Diabetes secondary to pancreatic disease accounts for 0.5% of all cases of diabetes mellitus. These conditions are associated with exocrine as well as endocrine pancreatic failure and present a complex management challenge. Diabetes in patients with haemochromatosis is associated with micro- and macrovascular complications and most patients require insulin therapy. Regular venesection to reduce the iron overload is associated with improvements in glycaemic control. Secondary haemochromatosis occurring in patients with haematological conditions requiring frequent blood transfusions is also associated with diabetes. Diabetes secondary to pancreatic disease is commonly seen and can present complex management problems which are best managed by a multidisciplinary team. Treating the underlying condition, as well as the associated hyperglycaemia, is essential.
Diabetes Secondary to Endocrine Disorders
Authors: Tomlinson Jeremy W.
Published: January 2022

Diabetes mellitus is associated with a variety of endocrine conditions affecting the pituitary, adrenal, and thyroid glands. It may occur as a consequence of hormonal excess (or less commonly deficiency) which interferes with either the secretion and/or the action of insulin. Diabetes is often diagnosed as part of the diagnostic work-up during an oral glucose tolerance test when glucose excursions can be measured alongside assessing the ability of a glucose load to suppress growth hormone levels. These associated conditions can include acromegaly, Cushing’s disease, hypo- and hyperthyroid, hyperaldosteronism, phaeochromocytoma, somatostatinoma, and glucagonoma.

While the principles of management may not differ (and include treating the underling endocrine disease), the fundamental importance lies in making the diagnosis so that appropriate treatment can be instigated without delay.
Type 2 Diabetes and Psychiatry
Authors: Calcia Marilia , Whicher Clare , Price Hermione , Ismail Khalida , Moulton Calum
Published: January 2022

Every category of mental disorders in the World Health Organization International Classification of Diseases 10th Revision (ICD-10) is associated with type 2 diabetes. Concurrent mental disorders add an additional £1.8 billion annually to the costs of type 2 diabetes care. This chapter will summarize those mental disorders most commonly associated with type 2 diabetes (depression, eating disorders, psychotic disorders, and dementia). Practical advice for non-specialists in recognizing these disorders and initiating first-line therapy will also be given. Finally, novel interventions to achieve better integration between mental and physical healthcare and improved biomedical outcomes and outlook for patients will be suggested.
Risks of Testosterone Treatment
Authors: Dobs Adrian , Yalamanchi Swaytha
Published: January 2022

Testosterone has been increasingly prescribed in recent years, particularly for middle-aged and older men with relatively non-specific symptoms that mimic androgen deficiency. There has thus been considerable interest in understanding the risk–benefit ratio of testosterone treatment in older men who may be particularly vulnerable to some of the adverse effects of exogenous testosterone. The exact risks and patient-important benefits are currently unknown due to lack of data from adequate randomized control trials, but some helpful inferences can be made based on available data. Erythrocytosis, the most commonly reported adverse effect of testosterone therapy, has been reported to be 3–4 times more likely in men treated with testosterone as compared to placebo; however, the form of therapy may play a role with the highest risk seen in men receiving intramuscular testosterone therapy as compared to transdermal formulations. Reassuringly, current data do not demonstrate that exogenous testosterone causes de novo or worsens mild to moderate lower urinary tract symptoms; insufficient data exist in men with severe lower urinary tract symptoms as such men have usually been excluded from testosterone trials. Testosterone has not been demonstrated to cause prostate cancer, but is not recommended presently in men who either have a history of prostate cancer or are otherwise at high risk. The effects of testosterone treatment on cardiovascular disease risk are unknown. The majority of presently available data do not suggest an increased risk, but in the absence of adequately powered randomized controlled trials, caution in men with pre-existing cardiovascular disease is recommended. Overall, further data are needed to better understand both the benefits and risks of exogenous testosterone in older men.
Black hole mergers in compact star clusters and massive black hole formation beyond the mass gap
Authors: Rizzuto Francesco Paolo , Naab Thorsten , Spurzem Rainer , Arca-Sedda Manuel , Giersz Mirek , Ostriker Jeremiah Paul , Banerjee Sambaran
Published: January 2022

We present direct N-body simulations, carried out with nbody6+ + gpu, of young and compact low-metallicity (Z = 0.0002) star clusters with 1.1 × 105 stars, a velocity dispersion of ∼15 $\mathrm{km\, s^{-1}}$, a half-mass radius Rh = 0.6 pc, and a binary fraction of $10{{\ \rm per\,cent}}$ including updated evolution models for stellar winds and (pulsation) pair-instability supernovae (PSNe). Within the first tens of megayears, each cluster hosts several black hole (BH) merger events which nearly cover the complete mass range of primary and secondary BH masses for current LIGO-Virgo-KAGRA gravitational wave detections. The importance of gravitational recoil is estimated statistically during post-processing analysis. We present possible formation paths of massive BHs above the assumed lower PSN mass-gap limit ($45\, {\rm M}_\odot$) into the intermediate-mass black hole (IMBH) regime ($\gt 100\, {\rm M}_\odot$) which include collisions of stars, BHs, and the direct collapse of stellar merger remnants with low core masses. The stellar evolution updates result in the early formation of heavier stellar BHs compared to the previous model. The resulting higher collision rates with massive stars support the rapid formation of massive BHs. For models assuming a high accretion efficiency for star–BH mergers, we present a first-generation formation scenario for GW190521-like events: a merger of two BHs which reached the PSN mass-gap merging with massive stars. This event is independent of gravitational recoil and therefore conceivable in dense stellar systems with low escape velocities. One simulated cluster even forms an IMBH binary (153, 173 M⊙) which is expected to merge within a Hubble time.
Dark and luminous mass components of Omega Centauri from stellar kinematics
Authors: Evans Addy J , Strigari Louis E , Zivick Paul
Published: January 2022

We combine proper motion data from Gaia EDR3 and HST with line-of-sight velocity data to study the stellar kinematics of the ω Cen globular cluster. Using a steady-state, axisymmetric dynamical model, we measure the distribution of both the dark and luminous mass components. Assuming both Gaussian and Navarro–Frenk–White mass profiles, depending on the data set, we measure an integrated mass of ≲106 M⊙ within the ω Cen half-light radius for a dark component that is distinct from the luminous stellar component. For the HST and radial velocity data, models with a non-luminous mass component are strongly statistically preferred relative to a stellar mass-only model with a constant mass-to-light ratio. While a compact core of stellar remnants may account for a dynamical mass up to ∼5 × 105 M⊙, they likely cannot explain the higher end of the range. This leaves open the possibility that this non-luminous dynamical mass component comprises non-baryonic dark matter. In comparison to the dark matter distributions around dwarf spheroidal galaxies, the ω Cen dark mass component is much more centrally concentrated. Interpreting the non-luminous mass distribution as particle dark matter, we use these results to obtain the J-factor, which sets the sensitivity to the annihilation cross-section. For the data sets considered, the range of median J-factors is ∼1022−1024 GeV2 cm−5, which is larger than that obtained for any dwarf spheroidal galaxy.
The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes Is Consistent with Adaptations to the Human Host
Authors: Kumar Akhil , Goyal Nishank , Saranathan Nandhini , Dhamija Sonam , Saraswat Saurabh , Menon Manoj B , Vivekanandan Perumal
Published: January 2022

Depletion of CpG dinucleotides in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes has been linked to virus evolution, host-switching, virus replication, and innate immune responses. Temporal variations, if any, in the rate of CpG depletion during virus evolution in the host remain poorly understood. Here, we analyzed the CpG content of over 1.4 million full-length SARS-CoV-2 genomes representing over 170 million documented infections during the first 17 months of the pandemic. Our findings suggest that the extent of CpG depletion in SARS-CoV-2 genomes is modest. Interestingly, the rate of CpG depletion is highest during early evolution in humans and it gradually tapers off, almost reaching an equilibrium; this is consistent with adaptations to the human host. Furthermore, within the coding regions, CpG depletion occurs predominantly at codon positions 2-3 and 3-1. Loss of ZAP (Zinc-finger antiviral protein)-binding motifs in SARS-CoV-2 genomes is primarily driven by the loss of the terminal CpG within the motifs. Nonetheless, majority of the CpG depletion in SARS-CoV-2 genomes occurs outside ZAP-binding motifs. SARS-CoV-2 genomes selectively lose CpGs-motifs from a U-rich context; this may help avoid immune recognition by TLR7. SARS-CoV-2 alpha-, beta-, and delta-variants of concern have reduced CpG content compared to sequences from the beginning of the pandemic. In sum, we provide evidence that the rate of CpG depletion in virus genomes is not uniform and it greatly varies over time and during adaptations to the host. This work highlights how temporal variations in selection pressures during virus adaption may impact the rate and the extent of CpG depletion in virus genomes.
Root-specific Reduction of Cytokinin Perception Enhances Shoot Growth in Arabidopsis thaliana
Authors: Monden Kota , Kojima Mikiko , Takebayashi Yumiko , Suzuki Takamasa , Nakagawa Tsuyoshi , Sakakibara Hitoshi , Hachiya Takushi
Published: January 2022

Previous studies suggest that root-derived cytokinins (CKs) contribute to shoot growth via long-distance transport; therefore, we hypothesized that an increase in root-derived CKs enhances shoot growth. To verify this, we grafted Arabidopsis Col-0 (wild type, WT) scion onto rootstock originated from WT or a double-knockout mutant of CK receptors Arabidopsis histidine kinase 2 (AHK2) and AHK3 (ahk2-5 ahk3-7; ahk23) because this mutant overaccumulates CKs in the body probably due to feedback homeostasis regulation. The grafted plants (scion/rootstock: WT/WT and WT/ahk23) were grown in vermiculite pots or solid media for vegetative growth and biochemical analysis. The root-specific deficiency of AHK2 and AHK3 increased root concentrations of trans-zeatin (tZ)-type and N6-(Δ2-isopentenyl) adenine (iP)-type CKs, induced CK biosynthesis genes and repressed CK degradation genes in the root. The WT/ahk23 plants had significantly larger shoot weight, rosette diameter and leaves area than did the WT/WT plants. Shoot concentrations of tZ-type CKs showed increasing trends in the WT/ahk23 plants. Moreover, the root-specific deficiency of AHK2 and AHK3 enhanced shoot growth in the WT scion more strongly than in the ahk23 scion, suggesting that shoot growth enhancement could occur through increased shoot perception of CKs. In the WT/ahk23 shoots compared with the WT/WT shoots, however, induction of most of CK-inducible response regulator genes was not statistically significant. Thus we suggest that the root-specific reduction of CK perception enhances shoot growth only partly by increasing the amount of root-derived tZ-type CKs and their perception by shoots. The unknown mechanism(s) distinct from CK signaling would also be involved in the shoot growth enhancement.
Correlates of gambling and gambling problems among Rhode Island young adults: a cross-sectional study
Authors: Noel Jonathan K , Rosenthal Samantha R , Sammartino Cara J
Published: January 2022

Background

Numerous states in the USA have legalized sports betting due to recent legal decisions by the US Supreme Court. Here, sociodemographic correlates of current gambling and specific gambling activities associated with symptoms of gambling problems were identified.

Methods

Cross-sectional data were obtained from the 2020 Rhode Island Young Adult Survey (RIYAS). RIYAS participants (n = 540) were a convenience sample of 18 to 25 year olds who lived in Rhode Island for at least part of 2020. Data were collected from May to October 2020. Four gambling activities were assessed (i.e. sports betting; betting on races; gaming tables at a casino; poker machines at a casino). Logistic regression models assessed main effects.

Results

22.4% engaged in one or more gambling activities. 11.5% of participants had any gambling problems. Odds of gambling activities were higher among men; Black, Indigenous, People of Color; older young adults; and essential workers. Odds of gambling problems were 2.4 times higher among participants who engaged with sports betting.

Conclusions

Gambling activities are common among several population subgroups, and participation in sports betting may be a risk factor for the development of problem gambling. Comprehensive prevention policies are needed.
The Theatre of Entrepreneurship: Learning to Perform the Speculative Self in University Entrepreneurship Programs
Authors: Chen Victor Tan , Goldstein Jesse
Published: January 2022

How do colleges teach students to be entrepreneurial? For three years, we observed young entrepreneurs, most of them students at Virginia Commonwealth University. Drawing from interviews with 57 students and recent graduates and observations of entrepreneurship-related events, we argue that entrepreneurial training encourages students to embrace a future-oriented and relational form of human capital. This speculative self (1) requires a performed authenticity that conveys the individual’s passion and relatability; (2) emphasizes potential for scalability and growth; and (3) is oriented toward the expectations of investors. Much of this work happens through the performance of the startup pitch, a well-crafted narrative of personal and commercial awakening. This study highlights three aspects of entrepreneurship training. First, students are encouraged to pitch continuously, the pitch serving as a means of affirming one’s entrepreneurial identity. Second, students are trained to convey their devotion to their venture through a relatable narrative. Third, students learn to pitch for investors interested in their potential to become an investment with rapid market growth. This performance is not limited to university entrepreneurship programs, but speaks to a broader transformation of the ways that workers are asked to demonstrate their value to a world unsure about whether they are a worthwhile investment.
Hepatitis A Seroprevalence in Mogadishu, Somalia
Authors: Akbulut Ulas Emre , Arslan Ebubekir
Published: January 2022

Background

The hepatitis A virus (HAV) is the most frequent global causes of vaccine-preventable viral hepatitis. Since Somalia is regarded as highly endemic for hepatitis A, the hepatitis A vaccine was not included in the World Health Organization’s expanded immunization program. The purpose of this study was to determine the prevalence of hepatitis A infection in the Somalia capital, Mogadishu.

Methods

The serological results of 1153 individuals presenting to the Mogadishu Training and Research Hospital between January 2019 and January 2021 were examined retrospectively to evaluate the presence of anti-HAV IgG and IgM. The seroprevalence of anti-HAV IgG and IgM was analyzed on the basis of age and sex. The seroprevalence of anti-HAV IgG was also compared among the 11-year age group.

Findings

The seroprevalence of anti-HAV IgG and IgM did not vary significantly between the sexes. Overall, the seroprevalence of anti-HAV IgG was 67.6%. The percentage of seropositivity for anti-HAV IgG was highest in adults aged ≥41 years (88.9%) and lowest in children aged 1–2 years (29.4%). Estimated age at midpoint of population immunity was 5 years which is compatible high endemicity. In addition, a significant rate of hepatitis A infection was also observed in the adolescent age group.

Conclusions

This study confirms the high HAV endemicity in Mogadishu. These data will be useful towards planning preventive and control measures by improving the sanitation programs in Mogadishu. Furthermore, prospective studies are needed to confirm these findings and evaluate urban–rural heterogeneity.
Elastic Intramedullary Nails in the Treatment of Pediatric Length Unstable Femur Fractures
Authors: Ouillette Ryan J. , Bastrom Tracey P. , Newton Peter O. , Pennock Andrew T.
Published: January 2022

Background:

Elastic intramedullary nails (EINs) are the treatment of choice for school-age children (5 to 12) with diaphyseal femur fractures. Previous literature suggests that EINs are an effective treatment for stable fracture patterns, but may be inadequate for unstable fracture patterns. The purpose of this study was to evaluate whether patients with length unstable fractures had a higher complication rate than those with length stable fractures when treated with EINs.

Methods:

All patients with diaphyseal femur fractures treated with EINs over a 22-year period at a single institution were reviewed. Patients were excluded if they had a pathologic fracture, neuromuscular disorder, spinal cord injury with subsequent involvement of affected limb, metabolic bone disease, or if they did not have at least 6-month follow-up.

Results:

A total of 85 patients with 87 diaphyseal femur fractures treated with EINs were included in the study. In all, 57.5% of the fractures were categorized as length stable and 42.5% were length unstable. Fourteen percent of length stable patients had a residual angular deformity compared with 5.4% of the length unstable group (P=0.24). The length unstable group experienced more shortening at the fracture site than the patients in the length stable group (P=0.003), but no patient required further intervention for their shortening. Two patients in the length stable group experienced overgrowth >2 cm and required subsequent surgery. No relationship was observed between fracture pattern and frequency of complications (length stable 8% vs. length unstable 10.8%, P=0.69). Finally, the knee immobilizer group (10.7%) and the long leg cast group (18.2%) had significantly higher complication rates than the single leg spica cast group (0%, P<0.05).

Conclusions:

There was no significant difference in complication rate between length stable and unstable fractures treated with EINs. Adjunctive spica casting may be protective against postoperative complications. While fracture shortening was more likely in the length unstable group, it did not result in increased rate of limb length discrepancy at final follow-up.

Level of Evidence:

Level IV, Case Series.
Impact of bacterial infection and intestinal microbiome on colorectal cancer development
Authors: Sun Jun
Published: January 2022

Accumulating evidence suggests that intestinal bacteria play an important role in the pathogenesis of colorectal cancer (CRC). Due to the complexity of the intestinal microbiome, identification of the specific causative microbial agents in CRC remains challenging, and the search for the causative microbial agents is intense. However, whether bacteria or their products can induce inflammation that results in tumorigenesis or directly causes CRC in humans is still not clear. This review will mainly focus on the progress of bacterial infection and CRC, and introduce the microbial contribution to the hallmarks of cancer. This article uses Salmonella and its chronic infection as an example to investigate a single pathogen and its role in the development of CRC, based on laboratory and epidemiological evidence. The bacterial infection leads to an altered intestinal microbiome. The review also discusses the dysfunction of the microbiome and the mechanism of host–microbial interactions, for example, bacterial virulence factors, key signaling pathways in the host, and microbial post-translational modifications in the tumorigenesis. Colonic carcinogenesis involves a progressive accumulation of mutations in a genetically susceptible host leading to cellular autonomy. Moving forward, more human data are needed to confirm the direct roles of bacterial infection in CRC development. Insights into the inhibiting infection will help to prevent cancer and develop strategies to restore the balance between host and microorganisms.
Zoster Eye Disease Study: Rationale and Design
Authors: Cohen Elisabeth J. , Hochman Judith S. , Troxel Andrea B. , Colby Kathryn A. , Jeng Bennie H. ,   on behalf of The ZEDS Trial Research Group
Published: January 2022

Purpose:

The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS).

Methods:

ZEDS is a National Eye Institute–supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status.

Results:

Over approximately 4 years, over 400 study participants have been enrolled.

Conclusions:

ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.
When a Nontuberculous Mycobacterial Infection Reveals an Error of Immunity
Authors: Morreale Alessia , Dotta Laura , Vairo Donatella , Bazzana Tullia , Lougaris Vassilios , Soresina Annarosa , Plebani Alessandro , Giliani Silvia Clara , Porta Fulvio , Matteelli Alberto , Redaelli De Zinis Luca Oscar , Badolato Raffaele
Published: January 2022

We present an algorithm that may be applied in case of a diagnosis of pediatric nontuberculous mycobacterial disease to identify the patients who may require an immunologic assessment to discover a possible underlying immune system defect predisposing to their nontuberculous mycobacterial infections.
Mothers' Experiences of Pregnancy, Labor and Birth, and Postpartum During COVID-19 in the United States
Authors: Saleh Lisette , Canclini Sharon , Greer Karissa , Mathison Cheryl , Combs Shanna M. , Dickerson Beth , Collins Kiley
Published: January 2022

The purpose of this study was to gain insight into the experiences of women who gave birth in the United States during coronavirus disease-2019 (COVID-19). A mixed-methods study was performed using online surveys and interviews. Data were analyzed using descriptive statistics and interview transcripts were analyzed by thematic analysis resulting in major themes. Participants (n = 32) were women who had given birth on or after March 13, 2020. Of the participants, 34% experienced depression, 46% experienced mild to moderate anxiety, and 28% experienced severe anxiety symptoms. Four major themes emerged: expectations versus reality, early versus late COVID-19 experience, mental distress versus mental health, and healthcare policy versus COVID-19 confusion. Experiences varied based upon geographical location, parity, and proximity to support. Short and long-term effects of COVID-19 on participants and their families were recognized. It is important to acknowledge the confusion experienced in many aspects of the birthing experience due to developing or conflicting pandemic or popular media information. Aligning expectations through providing clear, up-to-date information is helpful in decreasing mental distress. Finally, the impact of COVID-19 highlighted the critical need for professional and focused familial support and follow-up for women experiencing pregnancy-related mental health symptoms.
Monitoring of new therapies for hemophilia
Authors: Fernandez-Bello Ihosvany
Published: January 2022

Nonreplacement therapies, such as emicizumab (Hemlibra, Roche) and other myriad of molecules are still under study as concizumab (and other anti-TFPI) and fitusiran are transforming the quality of life and treatment of this group of patients. So far, laboratory monitorization has not been an obligate condition for the use of these novel therapies, though in some cases like their combination with bypassing agents to control breakthrough/surgical bleeds may seek for laboratory assays to ensure a well tolerated and effective utilization withing these special scenarios. In the next pages, application of global coagulation assays, for example, thrombinography or rotational thrombelastography will be referred looking to the works of some groups from around the world including our own experience.
The application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia
Authors: Tang Haowei , Yuan Zhi , Li JingJie , Wang Qun , Fan Weijie
Published: January 2022

Background:

The role of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia remains unclear, we aimed to analyze this issue to provide evidences into the management of clinical pneumonia.

Methods:

We searched PubMed et al databases up to October 20, 2021 for the randomized controlled trials on the application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia. Related outcomes were extracted and analyzed. Review Manager 5.3 software was used for data analysis.

Results:

A total of 13 randomized controlled trials involving 1317 elderly patients (559 cases in the ambroxol hydrochloride + fiberoptic bronchoscopy group and 658 cases in the fiberoptic bronchoscopy group) with pneumonia were included. Meta-analyses indicated that the blood oxygen partial pressure [mean difference (MD) = 5.75, 95% confidence interval (CI) (3.80, 7.70)], blood oxygen saturation [MD = 6.43, 95% CI (4.39, 8.48)], oxygenation index [MD = 26.75, 95% CI (14.61, 38.89)] of experimental group was significantly higher than that of control group (all P < .001), the incidence of multiple organ failure [odds ratio = 0.42, 95% CI (0.31, 0.56), P < .001], mortality on day 28 [odds ratio = 0.44, 95% CI (0.33, 0.59)] of experimental group was significantly less than that of control group (all P < .001).

Conclusions:

The high-dose ambroxol hydrochloride combined with fiberoptic bronchoscopy is beneficial to improve the patient's blood gas indicators, and reduce mortality in elderly patients with severe pneumonia.
The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis
Authors: Conti Bellocchi Maria Cristina , Marconato Eugenio , Lamonaca Laura , Cattani Mottes Martina , Ciccocioppo Rachele , Carrara Silvia , de Pretis Nicolo’ , Gabbrielli Armando , Crinò Stefano Francesco , Frulloni Luca
Published: January 2022

The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.

A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.

Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild–moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.

The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting.
Association between liver stiffness measurement by transient elastography and chronic kidney disease
Authors: Chan Ya-Ju , Chang Shy-Shin , Wu Jenny L. , Wang Sen-Te , Yu Cheng-Sheng
Published: January 2022

Transient elastography or elastometry (TE) is widely used for clinically cirrhosis and liver steatosis examination. Liver fibrosis and fatty liver had been known to share some co-morbidities that may result in chronic impairment in renal function. We conducted a study to analyze the association between scores of 2 TE parameters, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), with chronic kidney disease among health checkup population.

This was a retrospective, cross-sectional study. Our study explored the data of the health checkup population between January 2009 and the end of June 2018 in a regional hospital. All patients were aged more than 18 year-old. Data from a total of 1940 persons were examined in the present study. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD-simplify-GFR) equation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2.

The median of CAP and LSM score was 242, 265.5, and 4.3, 4.95 in non-CKD (eGFR > 60) and CKD (eGFR < 60) group, respectively. In stepwise regression model, we adjust for LSM, CAP, inflammatory markers, serum biochemistry markers of liver function, and metabolic risks factors. The P value of LSM score, ALT, AST, respectively is .005, <.001, and <.001 in this model.

The LSM score is an independent factor that could be used to predict renal function impairment according to its correlation with eGFR. This result can further infer that hepatic fibrosis may be a risk factor for CKD.
MR imaging features of Lhermitte–Duclos disease
Authors: Zhang Han-wen , Zhang Yuan-qing , Liu Xiao-lei , Mo Yong-qian , Lei Yi , Lin Fan , Feng Yu-ning
Published: January 2022

Rationale:

Lhermitte–Duclos disease (LDD) is a rare tumor of the nervous system with a typical “tiger striped’” sign, but its features on functional magnetic resonance imaging (fMRI) are still inconclusive.

Patient concerns:

To explore the characteristics of LDDs using fMRI.

Diagnoses:

We report 3 cases of pathologically confirmed LDDs.

Interventions:

Three patients underwent brain tumor surgery.

Outcomes:

All the patients had a good prognosis.

Lessons:

Magnetic resonance spectroscopy and susceptibility-weighted imaging combined with conventional MRI can be used to better diagnose LDDs. Perfusion-weighted imaging is not specific for distinguishing cerebellar tumors. The combined application of fMRI and conventional MRI can improve the accuracy of LDD diagnoses.