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Melt ponds on Arctic sea ice affect the radiative balance of the region as they introduce darkening of the sea ice during the Arctic summer. The temporal extent and spatial extent of the ponding, as well as its amplitude, reflect the state of Arctic sea ice and are important for our understanding of Arctic sea ice change. Remote sensing retrievals of melt pond fraction (MPF) provide information on both the present state of the melt pond development and its change throughout the years, which is valuable information in the context of climate change and Arctic amplification. In this work, we transfer the earlier published Melt Pond Detector (MPD) remote sensing retrieval to the Ocean and Land Colour Instrument (OLCI) data on board the Sentinel-3 satellite and so complement the existing Medium Resolution Imaging Spectrometer (MERIS) MPF dataset (2002–2011) from Environmental Satellite (ENVISAT) with recent data (2017–present). To evaluate the bias of the MPF product, comparisons to Sentinel-2 MultiSpectral Instrument (MSI) high-resolution satellite imagery are presented, in addition to earlier published validation studies. Both MERIS and OLCI MPD tend to overestimate the small MPFs (ranging from 0 to 0.2), which can be attributed to the presence of water-saturated snow and sea ice before onset of ponding. Good agreement for the middle-range MPF (0.2–0.8) is observed, and the areas of exceptionally high MPF = 100 % are recognized as well. The earlier published MERIS MPFs (2002–2011) were reprocessed using an improved cloud clearing routine and together with recent Sentinel-3 data provide an internally consistent dataset, which allows the MPF development in the past 20 years to be analyzed. Although the total summer hemispheric MPF trend is moderate, at +0.75 % per decade, the regional weekly MPF trends display a pronounced dynamic and range from −10 % to as high as +20 % per decade, depending on the region. We conclude the following effects: The global Arctic melt onset shifted towards spring by at least 2 weeks, with the melt onset happening in late May in recent years as compared to early June to mid-June in the beginning of the dataset. There has been a change in the pond onset regime in recent years, with the East Siberian and Laptev Sea dominating the melt onset and not the Beaufort Gyre region as before. The central Arctic, north Greenland and the Canadian Arctic Archipelago (CAA) have shown signs of increasing first-year ice (FYI) fraction in recent years. The daily gridded MPF averages are available on the web page of the Institute of Environmental Physics, University of Bremen, as a historic dataset for the ENVISAT data and as ongoing operational processing for the Sentinel-3 data.

Study abroad is often hailed as a unique and important learning experience that fosters students' ability to engage in effective and appropriate interactions in a variety of cultural contexts. Scholars, however, have not only questioned the learning that occurs in study abroad but have also highlighted problematic aspects such as the potential miseducation of participants and harm to host communities, particularly for short-term study abroad (STSA) experiences. Utilizing the lens of criticalhope, the purpose of this study was to critically assess the potential of STSA in fostering cross-cultural learning, while also examining its limitations and potential harm. Based on interviews with 18 participants 1 and 2 years after their STSA, we found STSA has the potential to be a catalyst for learning and growth related to the attitudes, knowledge, and skills needed for effective cross-cultural interactions. However, when participants approached STSA with a colonial attitude and failed to connect learning to cross-cultural experiences after STSA, that learning was minimal and STSA reinforced ethnocentric viewpoints. Participants' race and ethnicity shaped their learning. Black, Indigenous, and People of Color participants who had positive experiences abroad felt inspired by STSA to seek out additional cross-cultural interactions, which led to further growth. The white participants who experienced more growth had passions and interests related to cultural learning prior to STSA and engaged in meaningful cross-cultural experiences after STSA. In our Implications section, we discuss ways to maximize the potential of STSA to foster cross-cultural learning and serve as a catalyst for social change.

BACKGROUND: Frontal craniotomies for a medial subfrontal approach necessitate crossing the frontal sinus. Large superior extensions of the frontal sinus into frontal bone can result in mucosal retention in a free craniotomy bone flap, leading to a delayed mucocele with significant associated morbidity. The authors describe an open-window craniectomy technique that permits mucosal removal under direct vision and maintains the inner table on the bone flaps inferior side, helping to seal off the sinus opening with a pericranial flap. OBSERVATIONS: An illustrative case involving a medial right frontal craniotomy for a third ventricle mass in a patient with a large superior extension of the frontal sinus into frontal bone is presented. After creating a free frontal bone flap, the inner table was drilled out to the margins of the frontal sinus cavity and any remaining mucosa was cleared. A portion of the inner table above the bone flaps inferior margin was left in place, resembling an open window when viewed from the inner table side. The remaining anterior and posterior wall of the flap inferiorly provided a matched surface for the opening into the remaining frontal sinus, which was covered by pericranium. Long-term follow-up indicated no major complications or delayed mucocele. LESSONS: The open-window craniectomy technique can be considered for frontal sinus violations in patients with large superior frontal bone extension.

Abstract Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have tumor-targeting potential. We modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by ATAC-seq and RNA-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. HNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound-healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue. Cornification was frequently found surrounding necrotic areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators activated the differentiation program in primary HNSCC cells. In HNSCC tissue, distinct cell differentiation states were found to create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon faithful HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection.

ABSTRACT Aims Atrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health‐related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse. Methods Post hoc analysis of the prospective, investigator‐initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF‐related oral anticoagulation (OAC), and/or AF‐symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA). HRQOL was measured using the EQ‐5D‐3L‐questionnaire (including EQ‐index/EQ‐VAS) at baseline and after 12 months using multivariable linear mixed models. AF symptom severity was assessed using the European Heart Rhythm Association classification and symptom severity score (EHRA score) categorizing patients with no/mild/severe/disabling AF‐related symptoms. Results A first episode of AF was detected in 261/2927 (8.9%) patients within 12 months after the index stroke and 227/2920 (7.8%) patients had AF and were anticoagulated at 12 months. HRQOL (measured by EQ‐index, n = 2495 patients) was higher in AF patients on OAC compared to AF patients without OAC at 12 months after stroke (mean difference: MD: –16.8, 95% CI: 5.6 to 28.0), and similar in AF patients under OAC compared with patients without AF (MD: 2.0, 95% CI: –2.2 to 6.3). AF‐related symptoms were negatively associated with HRQOL (measured by EQ‐index) indicating that stroke patients with AF‐related symptoms had a lower HRQOL compared to asymptomatic AF patients (mild vs. asymptomatic: MD: –9.0, 95% CI: –17.7 to –0.3; severe/disabling vs. asymptomatic: MD: –19.1, 95% CI: –34.7 to –3.4). Discussion Stroke patients with newly diagnosed AF are at risk of lower quality of life at 12 months, depending on OAC status and AF symptom severity.

The impact of a slightly modified broadband snow surface albedo parameterization, which explicitly considers the cloud dependence of the snow albedo, is evaluated in simulations of a coupled regional climate model of the Arctic. The cloud dependence of the snow albedo leads to a more realistic simulation of the variability of the surface albedo during the snowmelt period in late May and June. In particular, the reproduction of lower albedo values under cloud-free/broken-cloud conditions during the snowmelt period represents an improvement and results in an earlier disappearance of the snow cover and an earlier onset of sea-ice melt. In this way, the consideration of the cloud dependence of the snow albedo results in an amplification of the two-stage snow/ice albedo feedback in the model. This finds expression in considerably increased sea-ice melt during the summer months and ends up in a new quasi-stationary equilibrium in sea ice with statistically significant lower sea-ice volume and statistically significant lower summer sea-ice area.

Introduction: Increasing evidence suggests that inflammation may play a pivotal role in the development of chronic pain and fatigue in aging individuals. This study investigated the relationship between three inflammatory markers (IL-6, CRP, and TNFα) and pain and fatigue, both cross-sectionally and longitudinally, in a sample of older adults from the Saint Louis Personality and Aging (SPAN) study. Methods: SPAN study participants provided blood samples at two in-person sessions approximately 2 years apart for the analysis of the inflammatory biomarkers IL-6, CRP, and TNFα. Pain and fatigue were assessed using the RAND-36 Health Status Inventory. Correlations (with false discovery rate correction for multiple testing) and follow-up linear regressions including potentially confounding demographic (e.g., annual household income) and health (e.g., BMI, medication use) covariates were used to estimate cross sectional and longitudinal associations. Analytic ns ranged from 533 to 815. Results: Cross-sectional analyses revealed that higher IL-6 and CRP were associated with greater reported pain and fatigue, even after accounting for covariates (βs > .098, ps .12, ps

Patients with space-occupying lesions adjacent to the superior sagittal sinus (SSS) present several technical considerations. For craniotomies crossing the SSS, a two-part method allows for dissection of the epidural space and dura under direct vision after removing a more lateral parasagittal bone flap. However, when the inner table surface of the medial component of the two-part bone flap is irregular, this can be difficult. We describe a method for channel drilling of the diploic bone, which allows for the piecemeal removal of the inner table using an upbiting rongeur. This article presents the case of meningioma with documented growth and provides a technical note of this technique to facilitate safe dissection of the midline dura. A patient presented with headaches and an anterior one-third parasagittal meningioma with documented growth. She selected surgical removal for treatment. A right frontal two-part parasagittal craniotomy was recommended. The preoperative imaging showed that the frontal bone was thick, with irregularity of the inner table. Intraoperatively, a channel was drilled in the diploic space of the bone, leaving the outer table intact. This provided a thin lip of the inner table that could be dissected over a short distance and then removed with a 2-mm upbiting rongeur. This allowed for further dissection of the dura crossing the midline under direct vision and safe secondary bone piece removal. The dura was opened to the edge of the SSS, allowing full exposure of the parasagittal region and interhemispheric fissure, thus limiting retraction of the medial right frontal lobe. The bone flap was removed in two pieces without a dural tear over the midline in spite of inner table irregularities. A Simpson grade 1 removal was accomplished, including excision of the affected falx, and the postoperative course was uncomplicated. In conclusion, diploic bone channel drilling is a technique that can be used to create a thin lip of the inner table, which can be removed piecemeal for safe dissection of the midline dura crossing the midline.

Without prompt diagnosis and treatment, patients with Lyme disease may develop life threatening multi-organ system complications. As such, we discuss the key diagnostic features of the condition along with patient-specific suggested treatment protocols. Additionally, Lyme disease is reportedly expanding to regions that were previously not impacted, key epidemiological features are outlined. We discuss a patient with severe Lyme disease who presented with widespread cutaneous involvement and atypical pathologic findings within an uncharacteristic geographic region. Erythematous, annular patches and plaques with dusky-to-clear centers were initially observed on the right thigh and later extended to the trunk and bilateral lower extremities. The diagnosis of Lyme disease was made clinically and confirmed with western blot testing that was positive for IgM antibodies. The patient additionally had a history of rheumatoid arthritis, for which he discontinued treatment prior to the current presentation with Lyme disease. During follow up visits, the patient noted lower extremity joint pain. Due to the overlapping clinical features of post-Lyme arthritis and rheumatoid arthritis, key differences are outlined to prevent misdiagnosis. Data revealing trends in the geographic distribution of the disease and possible need for increased surveillance and prevention strategies within previously unaffected areas are discussed.

Virtual exchanges (VEs) are course-based experiences designed to promote global learning, often by integrating cross-cultural interactions and collaborations with people from other areas of the world into coursework in a virtual format. Due to the widespread disruption of the COVID-19 pandemic, VEs have seen an increase in popularity. However, research findings on the effectiveness of VEs are mixed, and limited guidance is available to VE instructors on how to structure and facilitate these programs. The purpose of this paper is to highlight how theories and literature in two distinct areas of scholarship, Intergroup Contact theory and the Community of Inquiry model in online learning, could be applied to VEs to maximize student learning. We discuss each of these theories first and then highlight how they could be applied to VEs using illustrative examples from a pilot study of five VE courses offered at one institution during the summer of 2021.

Hydrangea serrata, also knowen as the Japanese tea hortensia, is known for its sweet taste and health properties of bevarages produced from this plant. The H. serrata 3,4-dihydroisocoumarins, hydrangenol and phyllodulcin harbour a variety of biological activities and pharmacological properties. Therefore, a detailed understanding of dihydroisocoumarin biosynthesis in H. serrata is of major interest. Their biosynthesis is assumed to be enhanced by elicitors and mediated by polyketide synthases like in cases of phenylpropanoid derived phytoalexins. A de-novo transcriptome assembly of leaves and roots from the aluminium chloride treatment group versus the control group alongside with annotation was generated. Secondary plant metabolites were analysed by LC-MS. It revealed that a terpene synthase and a triterpenoid synthase gene as well as lignin biosynthesis encoding genes were upregulated in roots. Many genes for transporters, glycosyl, and other transferases as well as glycosylases were found to be differentially expressed in both organs. As no differentially expressed polyketide synthase gene homolog was found, the relative leaf and root 3,4-dihydroisocoumarin content was analysed by LC-MS measurement. Although Hydrangea species are known for their aluminium detoxification using phenylpropanoid-derived compounds, the levels of 3,4- dihydroisocoumarins were not enhanced. In this metabolite analysis, an organ- specific accumulation profile of hydrangenol, phyllodulcin, hydrangeic acid and their mono- and di-glycosides was figured out.

Here, we report an individual, eventually diagnosed with HMG-CoA synthase deficiency, who presented with a cyclic vomiting phenotype. HMG-CoA synthase deficiency is a rare disorder affecting ketone body synthesis in which affected individuals typically present at a young age with hypoketotic hypoglycemia, lethargy, encephalopathy, and hepatomegaly, usually triggered by catabolism (e.g., infection or prolonged fasting). This individual presented with recurrent episodes of vomiting and lethargy, often associated with hypoglycemia or hyperglycemia, at 3 years of age. Metabolic labs revealed nonspecific abnormalities in her urine organic acids (showing mild elevation of dicarboxylic acids with relatively low excretion of ketones) and a normal acylcarnitine profile. Given her clinical presentation, as well as a normal upper gastrointestinal series, esophagogastroduodenoscopy with biopsies, and abdominal ultrasound, she was diagnosed with cyclic vomiting syndrome at 3 years of age. Molecular testing completed at 7 years of age revealed a previously reported pathogenic sequence variant (c.1016+1G>A) and a novel likely pathogenic deletion (1.57 kB deletion, including exon 1) within HMGCS2 consistent with HMG-CoA synthase deficiency. This individual’s presentation, mimicking cyclic vomiting syndrome, widens the clinical spectrum of HMG-CoA synthase deficiency. In addition, this case highlights the importance of molecular genetic testing in such presentations, as this rare disorder lacks specific metabolic markers.

Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.

India’s biometric unique ID Aadhaar has been at the forefront of the global revolution in digital identification, and India’s most significant investment in state capacity over the past decade. Yet, its application to social protection programs has been controversial. Proponents claim that the use of Aadhaar to identify and authenticate beneficiaries in these programs has led to considerable fiscal savings, while critics claim that it has led to denial of benefits to the marginalized and caused substantial harm. We review research on the use and impact of Aadhaar in social programs in India over the last decade. Our main takeaway from the review is that biometric authentication has reduced leakage in multiple settings, but its impact on beneficiaries depends crucially on the protocols and details of implementation. We conclude with a list of policy suggestions for obtaining the benefits of Aadhaar while minimizing the risk of harm to beneficiaries.